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Review

Insecticidal Triterpenes in Meliaceae: Plant Species, Molecules and Activities: Part Ⅰ (Aphanamixis-Chukrasia)

by
Meihong Lin
1,
Sifan Yang
2,
Jiguang Huang
1,* and
Lijuan Zhou
1,*
1
Key Laboratory of Natural Pesticides and Chemical Biology, Ministry of Education, South China Agricultural University, Guangzhou 510642, China
2
Organic Agriculture, Wageningen University and Research, 6708 PB Wageningen, Gelderland, The Netherlands
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(24), 13262; https://doi.org/10.3390/ijms222413262
Submission received: 26 October 2021 / Revised: 24 November 2021 / Accepted: 6 December 2021 / Published: 9 December 2021
(This article belongs to the Section Molecular Plant Sciences)
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Abstract

:
Plant-originated triterpenes are important insecticidal molecules. The research on insecticidal activity of molecules from Meliaceae plants has always received attention due to the molecules from this family showing a variety of insecticidal activities with diverse mechanisms of action. In this paper, we discuss 102 triterpenoid molecules with insecticidal activity of plants of eight genera (Aglaia, Aphanamixis, Azadirachta, Cabralea, Carapa, Cedrela, Chisocheton, and Chukrasia) in Meliaceae. In total, 19 insecticidal plant species are presented. Among these species, Azadirachta indica A. Juss is the most well-known insecticidal plant and azadirachtin is the active molecule most widely recognized and highly effective botanical insecticide. However, it is noteworthy that six species from Cedrela were reported to show insecticidal activity and deserve future study. In this paper, a total of 102 insecticidal molecules are summarized, including 96 nortriterpenes, 4 tetracyclic triterpenes, and 2 pentacyclic triterpenes. Results showed antifeedant activity, growth inhibition activity, poisonous activity, or other activities. Among them, 43 molecules from 15 plant species showed antifeedant activity against 16 insect species, 49 molecules from 14 plant species exhibited poisonous activity on 10 insect species, and 19 molecules from 11 plant species possessed growth regulatory activity on 12 insect species. Among these molecules, azadirachtins were found to be the most successful botanical insecticides. Still, other molecules possessed more than one type of obvious activity, including 7-deacetylgedunin, salannin, gedunin, azadirone, salannol, azadiradione, and methyl angolensate. Most of these molecules are only in the primary stage of study activity; their mechanism of action and structure–activity relationship warrant further study.

Graphical Abstract

1. Introduction

Pesticides provide tremendous benefit to modern agriculture. It is well known that the increase of crop yields largely depends on synthetic pesticides. However, it is also recognized that synthetic pesticides have some negative impacts and the indiscriminate application of synthetic pesticides has resulted in contamination of water, soil, air, and crop products, etc. The persistent use of pesticides has also led to serious resistance and resurgence of insect pests [1]. The current consensus asserts that the development of new pesticides should be based on sustainable development, environmental protection, and ecological balance. In order to achieve sustainable development, many scientists have undertaken the search for low toxicity, low residue and environmentally friendly biopesticides, among which botanical pesticides are an important part. Botanical insecticides are attracting global attention as new tools to kill or suppress insect pest populations. Generally, natural products are particularly attractive as templates because of their structural diversity. They can be used directly and have been used as models for the development of several successful insecticides that introduce new mechanisms of action, which are greatly needed to overcome the acquired resistance to synthetic insecticide in agricultural production. Therefore, active chemicals isolated from plants are of considerable significance [2].
The Meliaceae family has 50 genera, including more than 550 species, which are evergreen or deciduous trees or shrubs and are mainly distributed in the tropics and subtropics. These plants are known to be rich sources of limonoids. Until now, various insecticidal active ingredients have been discovered in Meliaceae plants. Numerous studies have demonstrated that the great insecticidal potential of Meliaceae plants has been mainly due to triterpenoids. Many of these triterpenoids have shown contact poison, stomach poison, antifeedant, or growth inhibition activities on various important agricultural insects [3,4,5].
This review is an extensive coverage of naturally occurring insecticidal triterpenoids in eight genera (Aglaia, Aphanamixis, Azadirachta, Cabralea, Carapa, Cedrela, Chisocheton, and Chukrasia) of Meliaceae discovered from 1968 to the present. The insecticidal plant species, insecticidal phytochemicals and their structures, various insecticidal activities, the insecticidal mechanism of action, and the structure–activity relationship (SAR) of the active insecticidal chemicals are summarized. This review thus provides a relatively systemic background on the research of insecticidal triterpenoids from Meliaceae plants and can offer meaningful hints to the development of insecticidal triterpenoids as novel insecticides and promote the application of these molecules in agricultural production.

2. Structures of Triterpenes

Triterpenes are terpenoids derived from squalene, usually composed of 30 carbon atoms. The structural classification of triterpenoids is mainly grouped into six groups, including linear triterpenes, simple cyclic triterpenes (monocyclic triterpenes, bicyclic triterpenes, and tricyclic triterpenes), tetracyclic triterpenes, pentacyclic triterpenes, nortriterpenes, and triterpenoid saponins (Figure 1).
Tetracyclic triterpenes are mainly divided into five groups, including cycloartanes, cucurbitanes, dammaranes, lanostanes, tirucallanes, and protolimonoids; while pentacyclic triterpenoids are mainly divided into five groups, including friedelanes, hopanes, lupanes, oleananes, and ursanes. Simple cyclic triterpenes are further classified into three groups, including monocyclic triterpenes, bicyclic triterpenes, and tricyclic triterpenes. Additionally, triterpenoid saponoinsare saponins are formed by the linkage of hydroxyl groups at certain positions of triterpenoids with different kinds and quantities of sugars [6]. In particular, nortriterpenes are formed by the rearrangement and degradation of triterpenes. Nortriterpenes mainly include mononorterpenoids, dinorterpenoids, trinorterpenoids, tetranorterpenoids, and polynorterpenoids; among them, tetranortriterpenoids are generally found to show obvious insecticidal activities. Specifically, the skeleton of the Meliaceae plant is composed of 26 carbons with the loss of 4 carbons, therefore, they are also called tetranortriterpenoids.
Tetranortriterpenoids are well-known insecticidal limonoids formed by the loss of the four terminal carbons of the side chain in the apolipoprotein or apolipoane skeleton, and then cyclized to form a 17β-furan ring. The basic skeleton of limonoids undergoes oxidative rearrangement to form various types of limonoids. It is mainly divided into ring intact limonoids, ring-seco limonoids, rearranged limonoids, and limonoids derivatives [7].
Among them, ring intact limonoids are mainly classified into five types, including azadirones, cedrelones, havanensins, trichilins, and vilasinins. Particularly, azadirone limonoids are characteristic of 3-oxo-Δ1,2 and C-7 oxygenation, while the cedrelone limonoids are 5,6-enol-7-one derivatives. For havanensin limonoids, generally, there exist oxygenic substituents at C-1, C-3, and C-7, and the degree of oxidation of C-28 varies from methyl to carboxyl. In addition, most of the trichilin limonoids contain the C-19/29 lactol bridge and the 14,15-epoxide moieties, while the vilasinin limonoids have the characteristics of a 6α,28-ether bridge [8].
Ring-seco limonoids are mainly divided into demolition of a single ring (ring A-seco group, ring B-seco group, ring C-seco group, and ring D-seco group), demolition of two rings (rings A,B-seco group, rings A,D-seco group, and rings B,D-seco group), and demolition of three rings (rings A,B,D-seco group). In particular, the ring C-seco group, which belongs to the group of demolition of a single ring, can be further divided into five classes (azadirachtin/melia-carpin-class, azadirachtinin/meliacarpinin-class, salannin-class, nimbolinin-class, nimbin-class, and nimbolidin-class) [9], while the rings of the A,B-seco group, belonging to the group of demolition of two rings, can be further divided into prieurianin-class and others. In the prieurianin-class, aphanamixoid-type belong to its structural classification [10]. Similarly, rings B,D-seco group also can be further grouped into the andirobin-class and others.
Rearranged limonoids include 1,n-linkage group, 2,30-linkage group, 8,11-linkage group (namely, trijugin-class), 10,11-linkage group (namely, cipadesin-class), and other linkages groups. Among them, 2,30-linkage groups include mexicanolides and phragmalins, and phragmalins can be further divided intophragmalinorthoesters and polyoxyphragmalins.
In addition, limonoid derivatives contain seven types, which are pentanortriterpenoids, hexanortriterpenoids, heptanortriterpenoids, octanortriterpenoids, enneanortriterpenoids, N-containing derivatives, and simple degraded derivatives [9].

3. Plant Species and Their Insecticidal Chemicals

A total of 19 insecticidal plant species from eight genera (Aglaia, Aphanamixis, Azadirachta, Cabralea, Carapa, Cedrela, Chisocheton, and Chukrasia) in Meliaceae are reported here to show insecticidal activities (Table 1 and Figure 2). In these species, Azadirachta indica A. Juss was the most well-known insecticidal plant and azadirachtin was the active molecule most widely recognized and highly effective botanical insecticide [10,11,12,13,14,15,16]. However, it is noteworthy that six species from Cedrela were reported to show insecticidal activity, deeming them deserving of further study.
In total, 102 insecticidal chemicals were found to be active from the 19 aforementioned plant species. They were active on 29 insect species (Aedes aegypti (L.), Aedes albopictus Skuse, Anopheles gambiae Giles, Anopheles stephensi Liston, Atta sexdens rubropilosa Forel, Culex quinquefasciatus Say, Diabrotica balteata Le Conte, Epilachna paenulata Germar, Epilachna varivestis Mulsant, Helicoverpa armigera (Hübner), Heliothis virescens (Fabricius), Heliothis zea (Boddie), Leptinotarsa decemlineata (Say), Locusta migratoria (L.), Musca domestica L., Ostrinia nubilalis (Hübner), Pectinophora gossypiella (Saund.), Peridroma saucia (Hübner), Phyllotreta striolata (Fabricius), Pieris brassicae (L.), Pieris rapae (L.), Plutella xylostella (L.), Reticulitermes speratus Kollbe, Rhodnius prolixus Stål, Schistocerca gregaria Forskål, Sitobion avenae (Fabricius), Spodoptera frugiperda Smith, Spodoptera littoralis (Boisduval), and Spodoptera litura (F.)). Generally, these plant-derived chemicals showed good antifeedant, growth inhibition activity, poisonous activity as well as other activities [9,17,18,19,20,21,22,23,24,25,26,27,28,29,30].
In sum, 43 chemicals isolated from 15 plant species (Aphanamixis polystachya (Wall.) R. Parker, Azadirachta excelsa (Jack) Jacobs, A. indica A. Juss, Azadirachta siamensis Val., Cabralea canjerana (Vell.) Mart, Cabralea eichleriana DC., Carapa guianensis Aubl., Cedrela dugessi (S. W atson), Cedrela fissilis Vell., Cedrela odorata L., Cedrela salvadorensis L., Cedrela sinensis Juss., Chisocheton paniculatus Hiern., Chisocheton siamensis Craib, and Chukrasia tabularis A. Juss.) showed antifeedant activity against 16 insect species (E. paenulata, E. varivestis, H. armigera, L. decemlineata, L. migratoria, O. nubilalis, P. saucia, P. striolata, P. brassicae, P. rapae, P. xylostella, R. speratus, R. prolixus, S. gregaria, S. littoralis, and S. litura) (Table 2) [9,17,21,22,23,29,31]. In these chemicals, azadirachtin, namely azadirachtin A, was the most active and has been successfully used as a botanical insecticide. Azadirachtin B and L also showed significant activity. Normally, the widely used various neem-based insecticide preparations consisted of not only azadirachtin A but also other similar azadirachtins, such as azadirachtin B and L. Still, the activity of other azadirachtins and some other types of chemicals deserves more attention. For example, epoxyprieurianin showed an obvious antifeedant activity on H. armigera (EC50 = 3.2 μg/mL, 7 d). Another chemical, 1-tigloyl-3-acetyl-azadirachtol, showed good activity on E. varivestis. These chemicals could be developed as antifeedant agents on some specific insects in the future [9,32,33].
Overall, 49 chemicals isolated from 14 plant species (Aglaia elaeagnoidea (A. Juss.), A. polystachya, A. excelsa, A. indica, C. canjerana, C. eichleriana, C. guianensis, C. dugessi, C. fissilis, C. salvadorensis, C. sinensis, Chisocheton ceramicus (Miq.) C.DC., Chisocheton erythrocarpus Hiern, and C. paniculatus) in Meliaceae exhibited poisonous activity on 10 insect species (A. aegypti, A. albopictus, A. gambiae, A. stephensi, A. sexdens rubropilosa, C. quinquefasciatus, D. balteata, P. xylostella, S. frugiperda, and S. littoralis) (Table 3) [9,19,20,25,26,28,43]. Normally, the poisonous activity was not the most important of many plant-derived chemicals. However, azadirachtin did show good poisonous activity against S. littoralis. Other chemicals such as azadirachtin O, azadirachtin P, azadirachtin Q, azadirachtin B, azadirachtin L, azadirachtin M, 11α-azadirachtin H, and azadirachtol also showed good poisonous activity on P. xylostella, with LD50 (24 or 96 h) values ranging from 0.75 to 3.92 μg/g [9,33].
As a whole, 19 chemicals isolated from 11 plant species (A. elaeagnoidea, A. excelsa, A. indica, C. canjerana, C. guianensis, C. fissilis, C. odorata, C. salvadorensis, Cedrela toona Roxb., C. paniculatus, and C. siamensis) in Meliaceae possessed growth regulatory activity on 12 insect species (A. aegypti, H. armigera, H. virescens, H. zea, M. domestica, O. nubilalis, P. gossypiella, P. saucia, R. prolixus, S. frugiperda, S. littoralis, and S. litura) and some locusts (Table 4) [17,22,27,30,31,40,43]. Among these chemicals, azadirachtin was the most effective insect growth regulatory agent showing good activity on H. armigera, R. prolixus, H. zea, H. virescens, S. frugiperda, P. gossypiella, S. litura, and S. littoralis, with EC50 or ED50 values (7 or 10 d) ranging from 0.11 to 0.70 μg/mL [9,29,30,48,50].
The following sections describe the insecticidal plant species, the corresponding insecticidal chemicals, and their activities in detail.

3.1. Aglaia

In the Aglaia genus, two species, including A. elaeagnoidea and A. odorata, have been reported to show insecticidal activity. Previous phytochemical investigation and bioactivity studies on the Aglaia genus have shown the main chemical group of this genus to be rocaglamide derivatives (flavaglines) [53]. However, triterpenoids were also the main insecticidal active constituents in this genus.
6α-acetoxygedunin, belonging to ring D-seco limonoids, was isolated from A. elaeagnoidea and could reduce the growth of the European corn borer O. nubilalis at 50 μg/mL [17,51]. A. odorata has been reported to show insecticidal activity on the cotton leafworm S. littoralis [54,55]. However, most of the reported compounds with insecticidal activity extracted from this species were rocaglaol derivatives. In addition, some triterpenoids, such as eleganoside A and odoratanone A, have also been reported to be extracted from A. odorata, but their insecticidal activities have not been described [56,57,58].

3.2. Aphanamixis

Aphanamixis is a rich source of limonoids [59,60,61]. In this genus, A. polystachya and A. grandifolia have been reported to show insecticidal activity (Table 1).
A total of 17 tetranortriterpenoids were reported to show insecticidal activities. In detail, the 17 tetranortriterpenoids contained 13 rings A,B-seco-type limonoids (prieurianin, epoxyprieurianin, zaphaprinin I, zaphaprinin R, aphapolynin A, aphapolynin C, aphapolynin F, aphapolynin D, dregenana-1, aphanamixoid A, aphanamixoid C, aphanamixoid F, and aphanamixoid G) [18,31,62] and 4 ring A-seco type chemicals (aphanalide E, aphanalide F, aphanalide G, and aphanalide H) [19,34].

3.2.1. Rings A,B-seco Limonoids

In this group, 13 chemicals have been reported to show insecticidal activity and they were prieurianin, epoxyprieurianin, zaphaprinin I, zaphaprinin R, aphapolynin A, aphapolynin C, aphapolynin F, aphapolynin D, dregenana-1, aphanamixoid A, aphanamixoid C, aphanamixoid F, and aphanamixoid G). These chemicals were isolated from A. polystachya [17,31,62,63].
In these chemicals, prieurianin and epoxyprieurianin exhibited antifeedant activity against the cotton bollworm, H. armigera and the EC50 values were 18.8 μg/mL and 3.2 μg/mL, respectively, after 7 d [34]. Further study has shown that prieurianin-type limonoids, zaphaprinin I, showed strong insecticidal activities against the aphid S. avenae, with a mortality score of 99, which was the same with the positive control thiamethoxam. Both Zaphaprinin I and Zaphaprinin R showed strong insecticidal activities against the diamondback moth/cabbage moth, P. xylostella and both mortalities were scored as 99, which was the same with the positive control thiamethoxam [63].
Aphapolynin A has been found to cause a mortality score of 66 against the diamondback moth P. xylostella in a leaf-disk assay at 500 μg/mL. Mortality was assessed relative to untreated control wells, with wells showing significant levels of mortality scored as 99, and wells without significant mortality scored as 0 [19,64]. Similarly, aphapolynin C, aphapolynin D, aphapolynin F, and dregenana-1 were found to possess obvious insecticidal activity against the banded cucumber beetle, D. balteata in a leaf-disk assay at 500 μg/mL [19,34,65].
Aphanamixoids are a novel class of limonoids derived from prieurianin-type limonoids. Aphanamixoid A, aphanamixoid C (highly oxidized tetra-uridine), aphanamixoid F, and aphanamixoid G all affected the feeding activity of the cotton bollworm, H. armigera. The EC50 values of these compounds (24 h) were 0.015, 0.017, 0.008, and 0.012 μmol/cm2, respectively [18,31,66].

3.2.2. Ring A-seco Limonoids

Aphanalide E, aphanalide F, aphanalide G, and aphanalide H were found to cause mortalities scored as 33–99 against the banded cucumber beetle D. balteata in a leaf-disk assay at 500 μg/mL at 5–9 days. Mortality was assessed relative to untreated control wells, with wells showing significant levels of mortality scored as 99, and wells without significant mortality scored as 0 [19,64].

3.3. Azadirachta

In this genus, three species, A. indica, A. excels, and A. siamensis were reported to show insecticidal activity with triterpenoids.
A total of 36 tetranortriterpenoids (21 ring-seco limonoids and 15 ring intact limonoids), 7 pentanortriterpenoids (11α-azadirachtin H, azadirachtin I, azadirachtin L, azadirachtin M, azadirachtin P, nimbinene, and nimbandiol), 2 octanortriterpenoids (desfurano-6α-hydroxyazadiradione and desfuranoazadiradione), and 2 protolimonoids (meliantriol and odoratone) were reported to show insecticidal activities [9,22,23,24,26,27,32,33,35,39].
Specifically, the 21 ring-seco limonoids were mainly the demolition of a single ring, consisting of 18 ring C-seco limonoinds (12 azadirachtin/meliacarpin-class chemicals, 5 salannins, and 1 nimbin-class chemical), and 3 ring D-seco limonoids (gedunin, 7-deacetylgedunin and 6β-hydroxygedunin). Further, the 12 azadirachtin/meliacarpin-class chemicals were azadirachtin A, azadirachtin B, azadirachtin D, azadirachtin E, azadirachtin F, azadirachtin G, azadirachtin K, azadirachtin N, azadirachtin O, azadirachtin Q, azadirachtol, and 1-tigloyl-3-acetylazadirachtol. The 5 salannins were salannin, 3-deacetylsalannin, salannol, 3-O-acetyl salannol, and nimbolide. Additionally, the only nimbin-class chemical was 6-deacetylnimbin. As far as the 15 ring intact limonoids were concerned, they were 13 azadirones (nimocinolide, isonimocinolide, azadirone, 7-deacetylazadiradione, 7-deacetyl-17β-hydroxyazadiradione, 17β-hydroxyazadiradione, 23-O-methylnimocinolide, 7-O-deacetyl-23-O-methyl-7α-O-senecioylnimocinolide, nimocinol, 6α-O-acetyl-7- deacetylnimocinol, 22,23-dihydronimocinol, epoxyazadiradione, and azadiradione), and 2 other ring intact limonoids (azadiraindin A and meliatetraolenone) [9,22,23,24,26,27,32,33,35,39].

3.3.1. Ring C-seco Chemicals

In this group, 18 chemicals were reported to show insecticidal activity: azadirachtin A, azadirachtin B, azadirachtin D, azadirachtin E, azadirachtin F, azadirachtin G, azadirachtin K, azadirachtin N, azadirachtin O, azadirachtin Q, azadirachtol, 1-tigloyl-3-acetylazadirachtol, salannin, 3-deacetylsalannin, 3-O-acetyl salannol, salannol, 6-deacetylnimbin, and nimbolide [9,22,23,32,33,39].
Among these chemicals, azadirachtins were the most widely used botanical insecticides originating from A. indica [67,68,69] and A. excels [20,32,36]. Presently, azadirachtins contain 15 analogs, 10 of which (azadirachtin A, B, D, E, F, G, K, N, O, and Q) belong to azadirachtin/meliacarpin-class chemicals and 5 of which (11α-azadirachtin H, I, L, M, and P) belong to pentanortriterpenoids [70]. As far as the insecticidal activity was concerned, Azadirachtin A, B, L, O, P, Q, and M gained wide attention [9,33,39].
Normally, azadirachtin is referred to as azadirachtin A [9]. Azadirachtin A has a broad control spectrum. It was reported that azadirachtin A possessed strong insecticidal activities against more than 400 insect species in Lepidoptera, Hymenoptera, Coleoptera, and so on. Azadirachtin A has shown various activities, including antifeeding, growth inhibition, repellent, stomach poisoning, and sterilizing [10,11,12,13,14,15,16]. Particularly, antifeeding and growth inhibition activities were the most remarkable [71,72,73]. Azadirachtins and neem-based formulations included liquid type, pellet type, alginate-biosorbent, and so on [74,75]. Of note, there are more than 2000 references focusing on azadirachtins and several reviews on azadirachtins. Further information can be referred to in the papers by Mordue (1993), Kraus (1993), Ley (1994), and Devakumar (2009) [21,41,76,77,78,79,80,81,82,83,84,85,86,87].
3-O-acetyl salannol, salannol, and salannin have shown growth inhibitory activity on the cotton bollworm H. armigera and the tobacco cutworm S. litura. After 7 days, the EC50 values of them on H. armigera were 64.2, 79.7, and 86.5 μg/mL, respectively. Similarly, the EC50 values of them on S. litura were 65.6, 77.4, and 87.7 μg/mL, respectively [22]. Meanwhile, these three chemicals together with 3-deacetylsalannin were also reported to show antifeedant activity on insects. In a choice leaf disc bioassay, after 7 days, 3-O-acetyl salannol, salannol, and salannin reduced feeding by 50% in S. litura at 2.0, 2.3, and 2.8 µg/cm2, respectively [22]. Salannin also showed antifeedant activity on the lower subterranean termite R. speratus and the PC95 value was 203.3 μg/disc after 30 d. In contrast, 3-deacetylsalannin showed a weak antifeedant activity on R. speratus and the PC95 value was 1373.1 μg/disc after 30 d [23].
In this group, another chemical nimbolide, isolated from A. indica and A. excels, could inhibit the feeding of the Mexican bean beetle, E. varivestis. The EC50 value was 90 μg/mL [9,32,88]. Nimbin-class chemical 6-deacetylnimbin showed antifeedant activity on the lower subterranean termite R. speratus. The PC95 value was 1581.2 μg/disc after 30 days [23].

3.3.2. Ring D-seco Chemicals

In this group, three chemicals were reported to show insecticidal activity and they were gedunin, 7-deacetylgedunin, and 6β-hydroxygedunin.
Gedunin showed antifeedant activity on the lower subterranean termite R. speratus (PC95, 113.7 μg/disc) and growth inhibitory activity on the cotton bollworm H. armigera (EC50, 50.8 μg/mL) and the tobacco cutworm S. litura (EC50, 40.4 μg/mL). In contrast, the derivative of gedunin, 7-deacetylgedunin, was reported to show a weaker antifeedant activity on the lower subterranean termite R. speratus (PC95, 218.4 μg/disc) after 30 days. However, in artificial diet bioassays, 6β-hydroxygedunin showed better growth inhibitory activity on the cotton bollworm H. armigera (EC50, 24.2 μg/mL, 7 d) and the tobacco cutworm S. litura (EC50, 21.5 μg/mL, 7 d). This efficacy was higher in comparison to gedunin, the EC50 (7 d) of which on H. armigera and S. litura were 50.8 and 40.4 μg/mL, respectively [23,35].

3.3.3. Rings Intact Limonoids: Azadirones, Azadiraindin A and Meliatetraolenone

As mentioned above, there were 13 azadirones: azadirone, azadiradione, epoxyazadiradione, 7-deacetylazadiradione, 17β-hydroxyazadiradione, and 7-deacetyl-17β- hydroxyazadiradione, nimocinol, 22,23-dihydronimocinol, 6α-O-acetyl-7-deacetylnimocinol, nimocinolide, isonimocinolide, 23-O-methylnimocinolide, and 7-O-deacetyl-23-O-methyl-7α- O-senecioylnimocinolide.
Azadirone showed antifeedant activity against the Colorado potato beetle L. decemlineata with an antifeedant index of 11.6 ± 6.3 (100 μg/mL) (starved for 6 h and feed for 20 h) [37]. Azadiradione and epoxyazadiradione were also reported to show antifeedant activities to some extent against the diamondback moth P. xylostella [24]. Further, azadiradione, 7-deacetylazadiradione, and 7-deacetyl-17β-hydroxyazadiradione were isolated from the seeds of A. indica and they showed growth inhibitory activity against the tobacco budworm H. virescens and the EC50 values were 560, 1600, and 240 μg/mL, respectively. Similarly, 17β-hydroxyazadiradione also showed antifeedant activity and the PC95 value at the lower subterranean termite R. speratus was 235.6 μg/disc after 30 days [23].
Nimocinol, 6α-O-acetyl-7-deacetylnimocinol, 23-O-methylnimocinolide, and 7-O-deacetyl-23-O-methyl- 7α-O-senecioylnimocinolide poseessed insecticidal activity on the mosquito A. aegypti. The LC50 (24 h) values of them were 21.0, 83.0, 53.0, and 2.14 μg/mL, respectively [25,45].
Nimocinolide, isonimocinolide and 22,23-dihydronimocinol were also isolated from the fresh leaves of A. indica [26,27]. Nimocinolide and isonimocinolide affected the fecundity of the housefly M. domestica at 100–500 μg/mL and showed mutagenic properties in the mosquito A. aegypti. In contrast, 22,23-dihydronimocinol showed poisonous activity on the mosquito A. stephensi and the LC50 value was 60 μg/mL after 24 h [26].
Additionally, the other ring intact limonoids, azadiraindin A and meliatetraolenone, were reported to show insecticidal activity. Azadiraindin A showed antifeedant activities against the diamondback moth P. xylostella. The antifeedant rate was 28% at 2000 μg/mL after 48 h [24]. Meliatetraolenone, isolated from the leaves of A. indica, showed insecticidal activities against the mosquito A. stephensi and the LC50 value was 16 μg/mL after 24 h [44].

3.3.4. Pentanortriterpenoids

In this group, seven chemicals have been reported to show insecticidal activity and they were 11α-azadirachtin H, azadirachtin I, azadirachtin L, azadirachtin M, azadirachtin P, nimbinene, and nimbandiol. There were five kinds of azadirachtin analogs (11α-azadirachtin H, I, L, M, and P) that belonged to pentanortriterpenoids. 11α-azadirachtin H, azadirachtin L, azadirachtin M, and azadirachtin P, which were reported to have insecticidal activities, were isolated from the seed kernels of A. excelsa. The LD50 values (24 h) of these derivatives against the diamondback moth P. xylostella were 5.75, 10.27, 8.46, and 2.19 μg/g, respectively [33].
Nimbinene exhibited growth inhibitory activity on insects and the EC50 values of nimbinene on the cotton bollworm H. armigera and the tobacco cutworm S. litura were 391.4 and 404.5 μg/mL, respectively after 7 days [35]. Further, nimbandiol were found to show antifeedant activity on the lower subterranean termite R. speratus and the PC95 values was 254.4 μg/disc after 30 days [23].

3.3.5. Octanortriterpenoids

Desfurano-6α-hydroxyazadiradione, isolated from fresh leaves of A. indica, showed insecticidal activity on the mosquito A. stephensi and the LC50 value was 43 μg/mL after 24 h [39]. Comparatively, desfuranoazadiradione showed relatively weak antifeedant activity on the diamondback moth P. xylostella to some extent as demonstrated by the low mortality rate (39.6% after 48 h) at a high concentration (2000 μg/mL) [24].

3.3.6. Protolimonoids

Odoratone, isolated from the leaves of A. indica, showed insecticidal activities against the mosquito A. stephensi and the LC50 value was 154 μg/mL after 24 h [44]. Another protolimonoid isolated from this plant was meliantriol, found to be a feeding inhibitor preventing locust chewing [52].

3.4. Cabralea

In this genus, C. canjerana has been reported to show insecticidal activity.
From C. canjerana, 2 tetracyclic triterpenes (cabraleadiol and ocotillone) and 2 tetranortriterpenoids were isolated and shown to have insecticidal activity [41,48]. Particularly, cabraleadiol and ocotillone belonged to dammaranes, while 3-β-deacetylfissinolide was one of mexicanolides. Furthermore, the 2 tetranortriterpenoids consisted of 1 ring B, D-seco limonoid (methyl angolensate), and 1 rearranged limonoid (3-β-deacetylfissinolide) [40,48]. Other known compounds such as gedunin and 7-deacetoxy-7-oxogedunin (belonging to ring D-seco limonoids) were also contained in these plants [89].
Ocotillone and methyl angolensate showed antifeedant activity on the tobacco cutworm S. litura. At 1μg/cm2, the PFI (percentage feeding index) values (24 h) of the two chemicals were 44.5 and 65.3, respectively [40,41,90,91,92,93]. Additionally, they also showed insecticidal activity at 50 mg/kg with a mortality rate of 40% for the larva of the fall armyworm S. frugiperda after 7 d [48,94]. Cabraleadiol and 3-β-deacetylfissinolide affected the larval development on S. frugiperda. At 50 mg/kg, when treated by the method of semi-artificial diet, the larval phase was extended by 1.2 d [48].

3.5. Carapa

In this genus, until now, only C. guianensis has been reported to show insecticidal activity [95,96].
From this species, a ring D-seco limonoid β-photogedunin and a ring intact limonoid 17β-hydroxyazadiradione were reported to show insecticidal activity [17,97]. Particularly, 17β-hydroxyazadiradione belong to azadirones. Other known compounds such as gedunin and 7-deacetoxy-7-oxogedunin were also contained in these plants [28].
At 50 mg/kg, β-photogedunin, when treated by the method of semi-artificial diet, reduced the weight of pupa the fall armyworm S. frugiperda. Meanwhile, the mortalities caused by β-photogedunin on the larval and pupal of S. frugiperda were 53.3% and 20.0% (7 d), respectively. In contrast, gedunin at 50 mg/kg caused a mortality of 63.3% to the larval S. frugiperda after 7 d [48,93]. 17β-hydroxyazadiradione showed antifeedant activity on the lower subterranean termite R. speratus with a PC95 (95% protective concentrations, μg/disc) value (30 d) of 235.6 μg/disc [23,98,99].

3.6. Cedrela

In the genus Cedrela, six species, C. dugessi, C. fissilis, C. odorata, C. salvadorensis, C. sinensis, and C. toona have been reported to show insecticidal activity [100,101].
From these species, 25 tetranortriterpenoids (1 ring intact limonoid (cedrelone), 15 ring-seco limonoids, 9 rearranged limonoids) and 2 pentacyclic triterpenes (oleanolic acid and oleanonic acid) were reported to show insecticidal activity. Specifically, the 15 ring-seco limonoids included 10 ring D-seco type chemicals (gedunin, photogedunin epimer mixture, 6α-acetoxy-gedunin, 7-deacetylgedunin, photoacetic acid acetate mixture, 7-deacetoxy-7-oxogedunin, photogeduninepimeric mixture, photogeduninepimeric acetate mixture, photogedunin, and 1,2-dihydro-3β-hydroxy-7-deacetoxy-7-oxogedunin) [28,47,49,102], 4 rings A, D-seco type chemicals (11β,19-diacetoxy-l-deacetyl-l-epidihydronomilin, 11β-acetoxyobacunyl acetate, 11β-acetoxyobacunol and odoralide) [29], and 1 rings B,D-seco type chemical cedrelanolide I [44]. The nine rearranged limonoids consisted of eight mexicanolides (swietenolide, swietemahonolide, 3β-acetoxycarapin, 8β,14α-dihydroswietenolide, 3β,6-dihydroxydihydrocarapin, 3β-hydroxyindoline, xyloccensin K, cedrodorin) and cipadesin B, a chemical belonging to 10,11-linkage limonoids [29,103]. In contrast, the above-mentioned mexicanolides belong to the 2,30-linkage group.

3.6.1. The Ring Intact Limonoid: Cedrelone

Cedrelone showed no antifeedant effect. However, cedrelone could affect the development and reproduction of the variegated cutworm P. saucia. After 9 days of feeding, the EC50 value of growth inhibition of cedrelone on P. saucia was found to be 53.1 μg/mL. By injection to the 6th instar of P. saucia, cedrelone inhibited growth, delayed development, and resulted in considerable larval mortality [43,50,104,105].

3.6.2. Ring D-seco Limonoids

Gedunin, photogedunin epimer mixture, and photoacetic acid acetate mixture have shown insecticidal activity. The LC50 values (7 d) of these compounds against the fall armyworm S. frugiperda were shown to be 39, 10, and 8 μg/mL, respectively [47,49,97,105]. Photogedunin, 6α-acetoxy-gedunin, 7-deacetylgedunin, 7-deacetoxy-7-oxogedunin, and 1,2-dihydro-3β-hydroxy-7-deacetoxy-7-oxogeduni possessed insecticidal activity on the leaf-cutting ant, A. sexdens rubropilosa. At 100 μg/mL, the S50 values (S50—survival average 50% (S50)/d) of these chemicals on A. sexdens rubropilosa varied from 8 to 11 d [28,106]. When treated with photogeduninepimeric acetate mixture at 10 μg/mL, the survival rate of the fall armyworm S. frugiperda was 50%. However, the photogeduninepimeric mixture showed a higher activity, as shown by the 17% survival rate of S. frugiperda when treated at 10.0 μg/mL after 24 h [49].

3.6.3. Rings A,D-seco Limonoids and Rings B,D-seco Limonoids

At 1000 μg/mL, 11β,19-diacetoxy-l-deacetyl-l-epidihydronomilin, 11β-acetoxyobacunyl acetate, 11β-acetoxyobacunol, and odoralide showed antifeedant activity on the cotton leafworm S. littoralis [29]. At 50 μg/mL, cedrelanolide I exhibited a significant weight reduction on the European corn borer O. nubilalis [51].

3.6.4. The Rearranged Limonoids

8β,14α-dihydroswietenolide showed antifeedant activity on the cotton leafworm S. littoralis, which was active at 500 μg/mL. Swietemahonolide and 3β-acetoxycarapin possessed insecticidal activity on the leaf-cutting ant A. sexdens rubropilosa. At 100 μg/mL, both S50 values of swietemahonolide and 3β-acetoxycarapin were 8 d [103]. Swietenolide, xyloccensin K, cedrodorin, and 3β,6-dihydroxydihydrocarapinand 3β-hydroxydihydrocarapin showed antifeedant activity on the cotton leafworm S. littoralis at 1000 μg/mL [29].
As for the 10,11-linkage limonoid cipadesin B, it was reported to possess an effect on A. sexdens rubropilosa. At 100 μg/mL, the S50 values of cipadesin B on A. sexdens rubropilosa was 9 d [103].

3.6.5. Pentacyclic Triterpenes

The two pentacyclic triterpenes, oleanolic acid and oleanonic acid, belong to oleanane triterpenes. They were reported to possess an effect on A. sexdens rubropilosa and the S50 values of oleanolic acid and oleanonic acid at 100 μg/mL on this insect were 6 d and 8 d, respectively [103].

3.7. Chisocheton

Four species, C. ceramicus, C. paniculatus, C. siamensis, and C. erythrocarpus, have been reported to exhibit insecticidal activity.
From C. paniculatus, three ring intact limonoids, azadiradione, 7-deacetylazadiradione (namely, nimbocinol), chisocheton compound F, and 2 mexicanolides (14-deoxy-Δ14,15-xyloccensin K, 14-deoxyxyloccensin K), were reported to exhibit insecticidal activity. Particularly, the three chemicals belonged to azadirones. Azadiradione was isolated from the acetone/hexane (1:1) extract of the seeds of C. siamensis. Moreover, gedunin was also contained in this plant [38,46,107,108].
Azadiradione showed growth inhibitory activity on the tobacco budworm H. virescens. The EC50 value (EC50 value was the effective concentration of additive necessary to reduce larval growth to 50% of the control values) was 560 μg/mL. In addition, the EC50 of its alkaline hydrolysis product, 7-deacetylazadiradione, was 1600 μg/mL [27,30,109]. Chisocheton compound F, isolated from C. paniculatus, showed antifeedant activity against the large white butterfly P. brassicae [38].
Mexicanolides 14-deoxy-Δ14,15-xyloccensin K and 14-deoxyxyloccensin K, isolated from C. ceramicus and C. erythrocarpus, showed larvicidal activity on the mosquitoes A. aegypti, A. albopictus, and C. Quinquefasciatus. After 24 h, the LC50 values of 14-deoxy-Δ14,15-xyloccensin K on them were 10.2, 12.16, and 16.82 μg/mL, respectively; while the LC50 values of 14-deoxyxyloccensin K on them were 3.19, 3.01, and 3.64 μg/mL, respectively [46].

3.8. Chukrasia

C. tabularis has been reported to show insecticidal activity.
From this species, five rearranged limonoids, belonging to tetranortriterpenoids, were isolated. Specifically, they were phragmalins, which belonged to the 2,30-linkage group of the rearranged limonoids. The five chemicals were tabulalin, tabulalide A, tabulalide B, tabulalide D, and tabulalide E. They all showed antifeedant activity against the third instar larvae of the cotton leafworm S. littoralis. Among them, tabulalin and tabulalide D were active at 500 μg/mL. Tabulalides A, B, and E were active at 1000 μg/mL at 2–12 h after the treatment [42,110,111,112,113].

4. Structures and Structure–Activity Relationship (SAR) of the Insecticidal Chemicals

4.1. Structures of the Insecticidal Chemicals

In total, 102 insecticidal chemicals have been summarized, including 96 nortriterpenes, 4 tetracyclic triterpenes, and 2 pentacyclic triterpenes. The structures of the chemicals are shown in Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, Figure 12, Figure 13, Figure 14, Figure 15, Figure 16, Figure 17, Figure 18, Figure 19, Figure 20 and Figure 21.
The 96 nortriterpenes include 87 tetranortriterpenoids, 7 pentanortriterpenoids, and 2 octanortriterpenoids. Further, the 87 tetranortriterpenoids contain 17 ring intact limonoids, 53 ring-seco limonoids, and 17 rearranged limonoids. Specifically, the 53 ring-seco limonoids include 4 ring A-seco chemicals, 18 ring C-seco limonoids, 12 ring D-seco limonoids, 13 rings A,B-seco limonoids, 4 rings A,D-seco limonoids, and 2 rings B,D-seco limonoids. The 17 rearranged limonoids include 16 2,30-linkage limonoids and one 10,11-linkage limonoid.

4.2. Structure–Activity Relationship (SAR) of the Insecticidal Chemicals

Traditional insecticide discovery effectively contributes to the development of new insecticides but is limited by high costs and long cycles. Structure–activity relationship (SAR) methods were introduced to evaluate the activity of compounds virtually, which saves significant costs for determining the activities of the compounds experimentally [114].
An SAR study on the antifeedant effects and developmental delays of three different azadirachtin A derivatives against E. varivestis showed that the hydroxy group at C-11 is important for high mortality rates and a single bond between C-22 and C-23 increases the degree of efficiency. An exchange of the large ester group ligands at C-1 and C-3 with hydroxy groups in combination with a single bond between C-22 and C-23 and a hydroxy group at C-11 leads to high feeding activity and a degree of efficiency of about 100% [115]. Interestingly, another study aiming to understand the structure-related bioactivities of the limonoids based on the insect antifeedant and growth-regulating activities of 22 limonoids (both natural and their derivatives) against the tobacco cutworm, S. litura, indicated that the C-seco limonoids (azadirachtins A, B, D, H, and I) were the most effective compounds as a group, while the intact limonoids (cedrelone and its derivatives) were the least effective. The cyclohexenone A ring and the α-hydroxy enone group in the B ring appear to be important for antifeedant activity. The presence of a cyclohexenone or 1,2-epoxide in the A ring coupled with an α-hydroxy enone in the B ring correlated well with growth regulatory activity. An acetoxy at C-7 instead of α-hydroxy enone, and perhaps the carbonyl at C-16, increase growth regulatory activity. The absence of 14–15 epoxide may not drastically reduce antifeedant activity and growth regulatory activity [41].
Based on 25 limonoids isolated from the fruits of A. polystachya, including seven new prieurianin-type limonoids, aphapolynins C-I, and one new C3-C6 connected aphanamolide-type limonoid aphanamolide B, along with 17 known compounds, a structure–activity analysis revealed that the α,β-unsaturated lactone and 14,15-epoxy moieties were essential for insecticidal activity [19]. Further structure–activity relationship analysis of the aphanamixoids indicated that the olefinic bond, the Δ2,30 configuration, and the substituent at C-12 significantly affected the antifeedant potency [18]. Antifeedant effect comparison of prieurianin, prieurianin acetate, epoxyprieurianin, and epoxyprieurianin acetate revealed that, first, epoxy compounds are more efficacious and, second, that acetylation enhances the activity of these rings A,B-seco-type limonoids [34].
A structure–activity study based on 11 molecules (nimbandiol, 17-hydroxyazadiradione, deacetylnimbin, 17-epiazadiradione, deacetylsalannin, azadiradione, nimbin, and deacetylgedunin), gedunin, salannin, and epoxyazadiradione) revealed that the furan ring, αβ-unsaturated ketone, and hydroxyl group each played an important role in determining the antifeedant activity. Specifically, a hydroxyl group at C-7 increased the antifeedant activity of gedunin [23]. Later, a further structure–activity study revealed that a hydroxyl group at C-7 reduced the insect growth inhibitory activity and the antifeedant activity of azadiradione, while a hydroxyl group at C-17 increased the activity of azadiradione and 7-deacetylazadiradione. Compared with 7-deacetylazadiradione, the parent natural product contained hydroxyl groups at both the C-7 and C-17 positions, which might contribute to the activity [27,30,109]. Hydroxyl groups in other groups of limonoids were also found to influence biological activity. For example, acetylation or ketonization of the C-7 or C-l 2 hydroxyl groups in the trichilins rendered them inactive as antifeedants against larvae of the southern armyworm, S. eridania (Cramer). On the other hand, deacetylation of the C-1 acetate group in nomilin rendered it inactive as a growth inhibitor against larvae of the fall armyworm and the corn earworm [23,30]. Additionally, comparison of the activities of β-photogedunin and gedunin indicated that oxidation of the furan ring led to a decrease in insecticidal activity [48].
An SAR study of rearranged limonoids was also investigated. By comparision of the antifeedant activity of tabulalin, tabulalide D, tabulalide E, tabulalide A, chukvelutilide I, chukvelutilide N, chukvelutilide J, chukvelutilide K, chukvelutilide L, tabulalide B, chukvelutilides O, and chukvelutilides M on the third instar larvae of the cotton leafworm, S. littoralis, it was concluded that acylation of the 30-hydroxy group on the tricyclodecane ring system reduced activity [42,110,111,112,113].

5. Insecticidal Mechanism of Action

A study of the insecticidal mechanism of action (MOA) of triterpenoids mainly focused on the MOA of azadirachtin with few MOA studies on other molecules. For example, it was demonstrated that both rings A,B-seco-type limonoids aphapolynin C and aphanalide H inhibited a nicotine response with IC50 at 3.13 μg/mL (aphapolynin C) and 1.59 μg/mL (aphanalide H), respectively, and aphanalides H also inhibited a GABA response with IC50 at 8.00 μg/mL [19]. Currently, azadirachtin is widely recognized as one of the most promising plant compounds for pest control in organic agriculture and one of the best alternatives to conventional insecticides in IPM programs [71,116]. The MOA study of azadirachtin has been a hot topic. However, even after many years of study, the exact molecular mechanism of action of azadirachtin has yet to be fully understood [117,118]. So far, the principal azadirachtin action on insects could be categorized into four groups: effects on neuro-endocrine activity, effects on reproduction, anti-feedancy, and cellular and molecular effects [116].
The primary antifeeding effect of azadirachtin seems to be mediated by gustatory chemosensillas and linked to inhibition on the rate of firing of sugar-sensitive cells of the gustatory chemoreceptors by activating bitter sensitive gustatory cells [119,120,121]. An internal feedback mechanism called secondary antifeedancy, including a long-term reduction in food intake, and deleterious effects on different insect tissues (muscles, fat body, gut epithelial cells), has also been reported [122,123,124]. In addition, azadirachtin showed an agonistic effect on dopaminergic neurons and can induce aversive taste memory in Drosophila melanogaster, and such memory is regulated by dopaminergic signals in the brain resulting in inhibition of the proboscis extension response (PER) [125].
Azadirachtin is an antagonist of 20-hydroxyecdysone (20E) and juvenile hormone (JH), two principal hormones in insects. The major action of azadirachtin has been its effect on hemolymph ecdysteroid and JH titers by inhibition of the secretion of morphogenetic peptide hormone (PTTH) and allatotropins from the corpus cardiacum complex, resulting in the IGD effects such as a failure of adult emergence, reduced pupation, or malformation. Moreover, azadirachtin could influence the activity of ecdysone 20-monooxygenase, which is a cytochrome P450-dependant hydroxylase responsible for the conversion of the steroid hormone ecdysone to its more active metabolite, and 20E. Furthermore, azadirachtin can cause degenerative structural changes in the nuclei in all endocrine glands (prothoracic gland, corpus allatum, and corpus cardiacum) responsible for controlling molting and ecdysis in insects, which would contribute to a generalized disruption of neuroendocrine function [117,122]. It was reported that the inhibition of growth and development in the fruit fly, D. melanogaster, after azadirachtin treatment was similar to those caused by disruption of the IIS pathway. In addition, azadirachtin can inhibit the excitatory cholinergic transmission and partly block the calcium channel, and this might interfere with different endocrinological and physiological actions in insects [126].
Owing to the interference of azadirachtin with yolk protein synthesis and or its uptake into oocytes, azadirachtin reduced the fecundity and fertility of several insects [127]. Sterility effects in females due to interference with vitellogenin synthesis and uptake into oocytes were also reported. In males, azadirachtin significantly decreases the number of cysts and the apical nuclei within the cysts in D. melanogaster, thereby inhibiting spermiogenesis [128,129,130]. In addition, azadirachtin was found to alter reproductive behavior, mating behavior, and oviposition behavior [128,131].
Additionally, the molecular insecticidal mechanisms of azadirachtin have been investigated and several explanations have been presented. For instance, it was found that azadirachtin could induce apoptosis through caspase-dependent pathways and could also inhibit protein synthesis and release by binding to specific proteins (such as heat-shock protein, hsp 60), affected genes encoding key enzymes such as the gene encoding cytochrome oxidase-related proteins CYP307A1 and CYP314A1, which catalyze the 20-hydroxyecdysone [132], and the gene encoding JH epoxide hydrolase, responsible for JH degradation by hydrolyzing the epoxide of JH [133,134,135].
In sum, recent work has demonstrated the MOA of azadirachtin to be complex and is not yet fully understood. Therefore, continued research is needed to reveal the ultimate MOA.

6. Future Outlook

Research on the insecticidal activity of Meliaceae plants has always received considerable attention. Investigations of Meliaceae plants over the past decades have led to some significant achievements.
Azadirachtin is the most successful botanical insecticide among the active compounds extracted from Meliaceae. Accordingly, the progress of the worldwide application of azadirachtin in controlling insect pests is inspiring. The application of azadirachtin can control insects, and at the same time, be safe for non-target arthropods. Such work demonstrates the effectiveness of a phytochemical for sustainable pest control in contrast to any negative effects of synthetic insecticide use.
In addition to azadirachtin, some azadirachtin analogs have also demonstrated strong insecticidal activities. Moreover, some compounds in Meliaceae possess more than one type of favorable activity, such as 7-deacetylgedunin, salannin, gedunin, azadirone, salannol, azadiradione, and methyl angolensate; some of which have multiple activities (poisoning, antifeeding, or growth inhibition). Among them, 7-deacetylgedunin and gedunin can be extracted from many Meliaceae plants. However, they are still in the primary stages of research and further studies on these compounds are needed. Their activities on insects should be systemically evaluated as well as their effects on non-target organisms and the environment. It is expected that 7-deacetylgedunin, gedunin, and so on, could be important molecules for managing insect pests in the near future.
Most of the compounds with obvious activity are only in the primary stages of research, and their mechanism of action and structure–activity relationship warrant further study. Generally, tetranortriterpenoids have complex structures and are difficult to synthesize. Therefore, it is of considerable significance to study the synthesis of tetranortriterpenoids with outstanding activity in Meliaceae.

Funding

This work was funded by Science and Technology Planning Programs of Guangdong Province, China (2017A020208040).

Conflicts of Interest

Authors declare no conflict of interest.

References

  1. Dalvi, R.R.; Salunkhe, D.K. Toxicological implications of pesticides: Their toxic effects on seeds of food plants. Toxicology 1975, 3, 269–285. [Google Scholar] [CrossRef]
  2. Hubbard, M.; Hynes, R.K.; Erlandson, M.; Bailey, K.L. The biochemistry behind biopesticide efficacy. Sustain. Chem. Process. 2014, 2, 18. [Google Scholar] [CrossRef] [Green Version]
  3. Christenhusz, M.J.M.; Byng, J.W. The number of known plants species in the world and its annual increase. Phytotaxa 2016, 261, 201–217. [Google Scholar] [CrossRef] [Green Version]
  4. González-Coloma, A.; López-Balboa, C.; Reina, M.; Fraga, B.M. Triterpene-based plant defenses. Phytochem. Rev. 2011, 10, 245–260. [Google Scholar] [CrossRef] [Green Version]
  5. Alvarenga, N.; Ferro, E.A. Bioactive Triterpenes and Related Compounds from Celastraceae. Stud. Nat. Prod. Chem. 2005, 36, 635–702. [Google Scholar]
  6. Geng, S.S. Triterpene Chemistry; Chemical Industry Press: Beijing, China, 2008. [Google Scholar]
  7. Champagne, D.E.; Koul, O.; Isman, M.B.; Scudder, G.G.E.; Towers, G.H.N. Biological activity of limonoids from the rutales. Phytochemistry 1992, 31, 377–394. [Google Scholar] [CrossRef]
  8. Nakatani, M.; Iwashita, T.; Mizukawa, K. Trichilinin, a new hexacyclic limonoid from Trichilia roka. Heterocycles 1987, 26, 43–46. [Google Scholar] [CrossRef]
  9. Tan, Q.G.; Luo, X.D. Meliaceous limonoids: Chemistry and biological activities. Chem. Rev. 2011, 111, 7437–7522. [Google Scholar] [CrossRef] [PubMed]
  10. Carpinella, M.C.; Defago, M.T.; Valladares, G.; Palacios, S.M. Antifeedant and insecticide properties of a limonoid from Melia azedarach (Meliaceae) with potential use for pest management. J. Agric. Food Chem. 2003, 51, 369–374. [Google Scholar] [CrossRef] [PubMed]
  11. Koul, O.; Isman, M.B. Effects of azadirachtin on the dietary utilization and development of the variegated cutworm Peridroma saucia. J. Insect Physiol. 1991, 37, 591–598. [Google Scholar] [CrossRef]
  12. Kubo, I.; Klocke, J.A. Azadirachtin, insect ecdysis inhibitor. Agric. Biol. Chem. 1982, 46, 1951–1953. [Google Scholar]
  13. Garcia, E.S.; Azambuja, P.D.; Forster, H.; Rembold, H. Feeding and molt inhibition by azadirachtins A, B, and 7-acetyl-azadirachtin A in Rhodnius prolixus nymphs. Z. Naturforsch. C 1984, 39, 1155–1158. [Google Scholar] [CrossRef]
  14. Mordue, A.J.; Nasiruddin, M. Azadirachtin treatment and host-plant selection. In Proceedings of the 8th International Symposium on Insect-Plant Relationships, Wageningen, The Netherlands, 9–13 March 1992; Springer: Dordrecht, The Netherlands, 1992; Volume 49, pp. 176–178. [Google Scholar]
  15. Bohnenstengel, F.I.; Wray, V.; Witte, L.; Srivastavad, R.P.; Proksch, P. Insecticidal meliacarpins (C-seco limonoids) from Melia azedarach. Phytochemistry 1999, 50, 977–982. [Google Scholar] [CrossRef]
  16. Cui, C.; He, S.J. Application and development of azadirachtin. Technol. Dev. Chem. Ind. 2014, 5, 40–42. (In Chinese) [Google Scholar]
  17. Hofer, M.; Greger, H.; Mereiter, K. 6α-acetoxygedunin. Acta Crystallogr. Sect. E Struct. Rep. Online 2009, 65, 1942–1943. [Google Scholar] [CrossRef] [PubMed]
  18. Jie, Y.C.; Duo, Z.C.; Hong, P.H.; Kong, N.C.; Zhang, Y.; Di, Y.T.; Zhang, Q.; Hua, J.; Jing, S.X.; Li, S.L.; et al. Limonoids from Aphanamixis polystachya and their antifeedant activity. Nat. Prod. 2014, 77, 472–482. [Google Scholar]
  19. Zhang, Y.; Wang, J.S.; Wang, X.B.; Gu, Y.C.; Wei, D.D.; Guo, C.; Yang, M.H.; Kong, L. Limonoids from the fruits of Aphanamixis polystachya, (Meliaceae) and their biological activities. J. Agric. Food Chem. 2013, 61, 2171–2182. [Google Scholar] [CrossRef] [PubMed]
  20. Abdelgaleil, S.; Doe, M.; Nakatani, M. Rings B,D-seco limonoid antifeedants from Swietenia mahogani. Phytochemistry 2013, 96, 312–317. [Google Scholar] [CrossRef] [PubMed]
  21. Singh, G.; Rup, P.; Koul, O. Acute, sublethal and combination effects of azadirachtin and Bacillus thuringiensis toxins on Helicoverpa armigera (Lepidoptera: Noctuidae) larvae. Bull. Entomol. Res. 2007, 97, 351–357. [Google Scholar] [CrossRef]
  22. Koul, O.; Singh, G.; Singh, R.; Singh, J.; Daniewski, W.M.; Berlozecki, S. Bioefficacy and mode-of-action of some limonoids of salannin group from Azadirachta indica A. Juss and their role in a multicomponent system against lepidopteran larvae. J. Biosci. 2004, 29, 409–416. [Google Scholar] [CrossRef] [PubMed]
  23. Ishida, M.; Serit, M.; Nakata, K.; Juneja, L.R.; Kim, M.; Takahashi, S. Several antifeedants from neem oil, Azadirachta indica A. Juss., against Reticulitermes speratus Kolbe (Isoptera: Rhinotermitidae). Biosci. Biotechnol. Biochem. 2014, 56, 1835–1838. [Google Scholar] [CrossRef] [Green Version]
  24. Yan, Y.X.; Liu, J.Q.; Wang, H.W.; Chen, J.X.; Chen, J.C.; Chen, L.; Zhou, L.; Qiu, M.H. Identification and antifeedant activities of limonoids from Azadirachta indica. Chem. Biodivers. 2015, 12, 1040–1046. [Google Scholar] [CrossRef]
  25. Siddiqui, B.S.; Afshan, F.; Ghiasuddin; Faizi, S.; Naqvi, S.N.H.; Tariq, R.M. Two insecticidal tetranortriterpenoids from Azadirachta indica. Phytochemistry 2000, 53, 371–376. [Google Scholar] [CrossRef]
  26. Bina, S.S.; Farhana, F.A.; Naeem, H.S.; Naqvi, S.N.H.; Tariq, R.M. Two new triterpenoids from Azadirachta indica and their insecticidal activity. J. Nat. Prod. 2002, 65, 1216–1218. [Google Scholar]
  27. Siddiqui, S.; Faizi, S.; Mahmood, T.; Siddiqui, B.S. Two new insect growth regulator meliacins from Azadirachta indica A. Juss (Meliaceae). JACS 1986, 1, 1021–1025. [Google Scholar] [CrossRef]
  28. Ambrozin, A.R.P.; Leite, A.C.; Bueno, F.C.; Vieira, P.C.; Fernandes, J.B.; Bueno, O.C.; da Silva, M.F.G.F.; Pagnocca, F.C.; Hebling, M.J.A.; Bacci, M. Limonoids from andiroba oil and Cedrela fissilis and their insecticidal activity. J. Brazil. Chem. Soc. 2006, 17, 542–547. [Google Scholar] [CrossRef] [Green Version]
  29. Kipassa, N.T.; Iwagawa, T.; Okamura, H.; Doe, M.; Morimoto, Y.; Nakatani, M. Limonoids from the stem bark of Cedrela odorata. Phytochemistry 2008, 69, 1782–1787. [Google Scholar] [CrossRef]
  30. Lee, S.M.; Olsen, J.I.; Schweizer, M.P. 7-deacetyl-17β-hydroxyazadiradione, a new limonoid insect growth inhibitor from Azadirachta indica. Phytochemistry 1988, 27, 2773–2775. [Google Scholar] [CrossRef]
  31. Cai, J.Y.; Zhang, Y.; Luo, S.; Chen, D.Z.; He, H.P. Aphanamixoid A, a potent defensive limonoid, with a new carbon skeleton from Aphanamixis polystachya. Org Lett. 2012, 14, 2524–2527. [Google Scholar] [CrossRef]
  32. Kraus, W.; Maile, R. 1-tigloyl-3-acetylazadirachtol, a new limonoid from the marrango tree, Azadirachta excelsa Jack (Meliaceae). Indian Chem. Soc. 1997, 74, 870–873. [Google Scholar] [CrossRef]
  33. Kanokmedhakul, S.; Kanokmedhakul, K.; Prajuabsuk, T.; Panichajakul, S.; Panyamee, P.; Prabpai, S.; Kongsaeree, P. Azadirachtin derivatives from seed kernels of Azadirachta excelsa. J. Nat. Prod. 2005, 68, 1047–1050. [Google Scholar] [CrossRef] [PubMed]
  34. Koul, O.; Daniewski, W.M.; Multani, J.S.; Gumulka, M.; Singh, G. Antifeedant effects of the limonoids from Entandrophragma candolei (Meliaceae) on the gram pod borer, Helicoverpa armigera (Lepidoptera: Noctuidae). J. Agric. Food Chem. 2003, 51, 7271–7275. [Google Scholar] [CrossRef] [PubMed]
  35. Koul, O.; Multani, J.S.; Singh, G.; Daniewski, M.; Berlozecki, S. 6β-hydroxygedunin from Azadirachta indica. Its potentiation effects with some non-azadirachtin limonoids in neem against lepidopteran larvae. J. Agric. Food Chem. 2003, 51, 2937–2942. [Google Scholar] [CrossRef] [PubMed]
  36. Morgan, E.D.; Thornton, M.D. Azadirachtin in the fruit of Melia azedarach. Phytochemistry 1973, 12, 391–392. [Google Scholar] [CrossRef]
  37. Rodríguez, B.; Caballero, C.; Ortego, F.; Castaera, P. A new tetranortriterpenoid from Trichilia havanensis. J. Nat. Prod. 2003, 66, 452–454. [Google Scholar] [CrossRef] [PubMed]
  38. Shilpi, J.A.; Saha, S.; Lim, C.S.; Nahar, L.; Sarker, S.D.; Awang, K. Advances in Chemistry and Bioactivity of the Genus Chisocheton Blume. Chem. Biodivers. 2016, 13, 483–503. [Google Scholar] [CrossRef] [PubMed]
  39. Jennifer, M.A.; Simmonds, M.S.J.; Ley, S.V. Actions of azadirachtin, a plant allelochemical, against insects. Pestic. Sci. 1998, 54, 277–284. [Google Scholar] [CrossRef]
  40. Suresh, G.; Gopalakrishnan, G.; Wesley, D.; Singh, N.D.P.; Malathi, R.; Rajan, S.S. Insect antifeedant activity of the tetranortriterpenoids from the Rutales. A perusal of structural relations. J. Agric. Food Chem. 2002, 50, 4484–4490. [Google Scholar] [CrossRef]
  41. Govindachari, T.R.; Narsimhan, N.S.; Suresh, G.; Partho, P.D.; Gopalakrishnan, G.; Kumari, G.N.K. Structure related insect antifeedant and growth regulating activities of some limonoids. Chem. Ecol. 1995, 21, 1585–1600. [Google Scholar] [CrossRef] [PubMed]
  42. Nakatani, M.; Abdelgaleil, S.A.M.; Saad, M.M.G.; Huang, R.C.; Doe, M.; Iwagawa, T. Phragmalin limonoids from Chukrasia tabularis. Phytochemistry 2004, 65, 2833–2841. [Google Scholar] [CrossRef]
  43. Koul, O.; Isman, M.B. Toxicity of the limonoid allelochemical cedrelone to noctuid larvae. Entomol. Exp. Appl. 2011, 64, 281–287. [Google Scholar] [CrossRef]
  44. Siddiqui, B.S.; Afshan, F.; Gulzar, T.; Sultana, R.; Naqvi, S.N.H.; Tariq, R.M. Tetracyclic triterpenoids from the leaves of Azadirachta indica and their insecticidal activities. Chem. Pharm. Bull. 2003, 51, 415–417. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Siddiqui, B.S.; Afshan, F.; Faizi, S.; Naqvi, S.N.H.; Tariq, R.M. New insect-growth-regulator meliacin butenolides from the leaves of Azadirachta indica A. Juss. J. Am. Chem. Soc. 1999, 16, 2367–2370. [Google Scholar] [CrossRef]
  46. Chong, S.L.; Hematpoor, A.; Hazni, H.; Azirun, M.S.; Litaudon, M.; Supratman, U.; Murata, M.; Awang, K. Mosquito larvicidal limonoids from the fruits of Chisocheton erythrocarpus Hiern. Phytochem. Lett. 2019, 30, 69–73. [Google Scholar] [CrossRef]
  47. Cespedes, C.L.; Calderon, J.S.; Lina, L.; Aranda, E. Agric growth inhibitory effects onfall armyworm Spodoptera frugiperda of some limonoids isolated from Cedrela spp. (Meliaceae). J. Agric. Food Chem. 2000, 48, 1903–1908. [Google Scholar] [CrossRef] [PubMed]
  48. Sarria, A.L.F.; Soares, M.S.; Matos, A.P.; Fernandes, J.B.; Vieira, P.C.; Silva, M.F.G.F. Effect of triterpenoids and limonoids isolated from Cabralea canjerana and Carapa guianensis (Meliaceae) against Spodoptera frugiperda (JE Smith). Z. Natur. C 2011, 66, 245–250. [Google Scholar] [CrossRef] [PubMed]
  49. Cespedes, C.L.; Carlos, L.C.A.; Avila, J.G.; Marin, J.C.; Domínguez, M.; Torres, P.; Aranda, E. Natural compounds as antioxidant and molting inhibitors can play a role as a model for search of new botanical pesticides. Adv. Phytomed. 2006, 3, 1–27. [Google Scholar] [CrossRef]
  50. Koul, O. Feeding deterrence induced by plant limonoids in the larvae of Spodoptera litura (F.) (Lepidoptera, Noctuidae). Z. Angew. Entomol. 1983, 95, 166–171. [Google Scholar] [CrossRef]
  51. Jimenez, A.; Villarreal, C.; Toscano, R.A.; Cook, M.; Mata, R. Limonoids from Swietenia humilis and Guarea grandiflora (Meliaceae). Phytochemistry 1998, 49, 1981–1988. [Google Scholar] [CrossRef]
  52. Abhijit, J. Process development of pesticide production from Azadirachta Indica A. Juss. Int. J. Agric. 2012, 23, 2848–2854. [Google Scholar]
  53. Ngo, N.T.N.; Lai, N.T.D.; Le, H.C.; Nguyen, L.T.T.; Nguyen, L.H.D. Chemical constituents of Aglaia elaeagnoidea and Aglaia odorata and their cytotoxicity. Nat. Prod. Res. 2021, 11, 1893723. [Google Scholar] [CrossRef] [PubMed]
  54. Nugroho, B.W.; Edrada, R.A.; Wray, V.; Wittec, L.; Bringmannd, G.; Gehlinge, M.; Proksch, P. An insecticidal rocaglamide derivatives and related compounds from Aglaia odorata (Meliaceae). Phytochemistry 1999, 51, 367–376. [Google Scholar] [CrossRef]
  55. Yang, S.H.; Zeng, S.Y.; Zheng, L.S. Insecticidal active constituents from twig of Aglaia odorata. Chin. J. Zhong Cao Yao 2004, 11, 1207–1211. [Google Scholar]
  56. Liu, B.; Yang, L.; Xu, Y.K.; Liao, S.G.; Luo, H.R.; Na, Z. Two new triterpenoids from Gelsemium elegans and Aglaia odorata. Nat. Prod. Commun. 2013, 8, 1373–1376. [Google Scholar] [CrossRef] [PubMed]
  57. Robin, B.B.; Kathleen, D. Triterpenoids of Aglaia odorata. Configuration of trisubstituted epoxides. J. Chem. Soc. 1977, 5, 510–512. [Google Scholar]
  58. Cai, X.H.; Luo, X.D.; Zhou, J.; Hao, X.J. Compound representatives of a new type of triterpenoid from Aglaia odorata. Org. Lett. 2005, 7, 2877–2879. [Google Scholar] [CrossRef] [PubMed]
  59. Wang, G.W.; Jin, H.Z.; Zhang, W.D. Constituents from Aphanamixis species and their biological activities. Phytochem. Rev. 2013, 12, 915–942. [Google Scholar] [CrossRef]
  60. Wu, S.L.; Zou, Q.P.; Xie, X.Y.; Ren, J.J.; Zhang, F.; OuYang, J.R.; Yin, P.C.; Dong, F.W.; He, H.P. Two new triterpenoids from the fruits of Aphanamixis polystachya. J. Asian Nat. Prod. Res. 2021, 1–8. [Google Scholar] [CrossRef] [PubMed]
  61. Camero, C.M.; Vassallo, A.; De, L.M.; Temraz, A.; Tommas, N.D. Limonoids from Aphanamixis polystachya leaves and their interaction with Hsp90. Planta Med. 2018, 84, 964–970. [Google Scholar] [CrossRef] [Green Version]
  62. Chen, S.K.; Chen, B.Y.; Li, H. Flora of China; Science Press: Beijing, China, 1997; Volume 43, pp. 239–240. [Google Scholar]
  63. Zhang, Y.; Wang, J.S.; Gu, Y.C.; Wang, X.B.; Kong, L.Y. Diverse prieurianin-type limonoid derivatives from the fruits of Aphanamixis grandifolia and their absolute configuration determination. Tetrahedron 2014, 37, 6594–6606. [Google Scholar] [CrossRef]
  64. Wang, H.; Yang, Z.K.; Fan, Z.J.; Wu, Q.J.; Zhang, Y.J.; Mi, N.; Wang, S.X.; Zhang, Z.C.; Song, H.B.; Liu, F. Synthesis and insecticidal activity of N-tert-butyl-N, N′-diacylhydrazines containing 1,2,3-thiadiazoles. J. Agric. Food Chem. 2011, 59, 628–634. [Google Scholar] [CrossRef] [PubMed]
  65. Luo, X.D.; Wu, S.H.; Wu, D.G.; Ma, Y.B.; Qi, S.H. Novel antifeeding limonoids from Dysoxylum hainanense. Tetrahedron 2002, 58, 7797–7804. [Google Scholar] [CrossRef]
  66. Luo, S.H.; Luo, Q.; Niu, X.M.; Xie, M.J.; Zhao, X.; Schneider, B.; Gershenzon, J.; Li, S.H. Glandular trichomes of Leucosceptrum canum harbor defensive sesterterpenoids. Angew. Chem. 2010, 122, 4573–4577. [Google Scholar] [CrossRef]
  67. Jarvis, A.P.; Morgan, E.D.; Edwards, C. Rapid separation of triterpenoids from Neem seed extracts. Phytochem. Anal. 1999, 10, 39–43. [Google Scholar] [CrossRef]
  68. Nat, J.M.; Sluis, W.G.; De Silva, K.T.D.; Labadiea, R.P. Ethnopharmacognostical survey of Azadirachta indica A. Juss (Meliaceae). J. Ethnopharmacol. 1991, 35, 1–24. [Google Scholar] [PubMed]
  69. Biswas, K.; Chattopadhyay, I.; Banerjee, R.K. Biological activities and medicinal properties of neem (Azadirachta indica). Curr. Sci. Bangalore 2002, 82, 1336–1345. [Google Scholar]
  70. Xu, H.H.; Lai, D.; Zhang, Z.X. Research and application of botanical pesticide azadirachtin. J. South China Agric. Univ. 2017, 38, 1–11. [Google Scholar]
  71. Bezzar, B.R.; Kilani, M.S.; Maroua, F.; Aribi, N. Azadirachtin induced larval avoidance and antifeeding by disruption of food intake and digestive enzymes in Drosophila melanogaster (Diptera: Drosophilidae). Pestic. Biochem. Physiol. 2017, 143, 135–140. [Google Scholar] [CrossRef] [PubMed]
  72. Radhika, S.; Sahayaraj, K.; Senthil-Nathan, S.; Hunter, W.B. Individual and synergist activities of monocrotophos with neem based pesticide, Vijayneem against Spodoptera litura Fab. Physiol. Mol. Plant P. 2017, 101, 54–68. [Google Scholar] [CrossRef]
  73. Lucantoni, L.; Giusti, F.; Cristofaro, M.; Pasqualini, L.; Esposito, F.; Lupetti, P.; Habluetzel, A. Effects of a neem extract on blood feeding, oviposition and oocyte ultrastructure in Anopheles stephensi Liston (Diptera: Culicidae). Tissue Cell 2006, 38, 361–371. [Google Scholar] [CrossRef]
  74. Lynn, O.M.; Song, W.G.; Shim, J.K.; Kim, J.E.; Lee, K.Y. Effects of azadirachtin and neem-based formulations for the control of sweetpotato whitefly and root-knot nematode. J. Korean Soc. Appl. Biol. 2010, 53, 598–604. [Google Scholar] [CrossRef]
  75. Flores, C.F.; Martínez, D.G.P.; Villafranca, S.M.; Pérez, M.F. Preparation and characterization of azadirachtin alginate-biosorbent based formulations: Water release kinetics and photodegradation study. J. Agric. Food Chem. 2015, 63, 8391–8398. [Google Scholar] [CrossRef] [PubMed]
  76. Mordue, A.J.; Blackwell, A. Azadirachtin: An update. J. Insect Physiol. 1993, 39, 903–924. [Google Scholar] [CrossRef]
  77. Devakumar, C.; Kumar, R. Total synthesis of azadirachtin: A chemical odyssey. Curr. Sci. 2009, 95, 573–575. [Google Scholar]
  78. Ley, S.V. Synthesis and chemistry of the insect antifeedant azadirachtin. Pure. Appl. Chem. 1994, 66, 2099–2102. [Google Scholar] [CrossRef]
  79. Kraus, W.; Bokel, M.; Schwinger, M. The chemistry of azadirachtin and other insecticidal constituents of Meliaceae. Proceedings 1993, 34, 18. [Google Scholar]
  80. Govindachari, T.R.; Sandhya, G.; Raj, S.P.G. Azadirachtins H and I: Two new tetranortriterpenoids from Azadirachta indica. J. Nat. Prod. 1992, 55, 596–601. [Google Scholar] [CrossRef]
  81. Rembold, H. The azadirachtins—Their potential for insect control. Econ. Med. Plant Res. 1989, 3, 57–72. [Google Scholar]
  82. Hummel, H.E.; Hein, D.F.; Schmutterer, H. The coming of age of azadirachtins and related tetranortriterpenoids. J. Biopest 2012, 5, 82. [Google Scholar]
  83. Rembold, H. The Azadirachtins: Potent insect growth inhibitors. Mem. Inst. Oswaldo Cruz 1987, 82, 61–66. [Google Scholar] [CrossRef] [Green Version]
  84. Ley, S.V.; Anderson, J.C.; Blaney, W.M.; Morgan, E.D.; Sheppard, R.N.; Sunmonds, M.S.J.; Slawm, A.M.Z.; Snuth, S.C.; Wllhamsa, D.J.; Wood, A. Chemistry of insect antifeedants from Azadirachta indica (part 11): Characterisation and structure activity relationships of some novel rearranged azadirachtins. Tetrahedron 1991, 47, 9231–9246. [Google Scholar] [CrossRef]
  85. Thompson, D.G.; Tonon, A.; Beltran, E.; Felix, H. Inhibition of larval growth and adult fecundity in Asian long-horned beetle (Anoplophora glabripennis) exposed to azadirachtins under quarantine laboratory conditions. Pest Manag. Sci. 2018, 74, 1351–1361. [Google Scholar] [CrossRef] [PubMed]
  86. Sinha, S.; Walia, S.; Kumar, J.; Panwar, V.P.S.; Parmar, B.S. Egg hatching inhibitory activity of Azadirachtins A, B and H against maize stem borer Chilo Partellus (Swinhoe). Pestic. Res. J. 2005, 17, 6–9. [Google Scholar]
  87. Govindachari, T.R.; Suresh, G.; Geetha, G.; Wesley, S.D. Insect antifeedant and growth regulating activities of neem seed oil-the role of major tetranortriterpenoids. J. Appl. Entomol. 2000, 124, 287–291. [Google Scholar] [CrossRef]
  88. Cui, B.; Chai, H.; Constant, H.L.; Santisuk, T.; Reutrakul, V.; Beecher, C.W.W.; Farnsworth, N.R.; Cordell, G.A.; Pezzuto, J.M.; Kinghorn, A.D. Limonoids from Azadirachta excelsa. Phytochemistry 1998, 47, 1283–1287. [Google Scholar] [CrossRef]
  89. Madhusudana, R.M.; Meshulam, H.; Zelnik, R.; Lavie, D. Structure and stereochemistry of limonoids of Cabralea eichleriana. Phytochemistry 1975, 14, 1071–1075. [Google Scholar] [CrossRef]
  90. Braga, P.; Soares, M.S.M.; Fátima, G.F.; Vieira, P.C.; Fernandes, J.B.; Pinheiro, A.L. Dammarane triterpenes from Cabralea canjerana (Vell.) Mart. (Meliaceae): Their chemosystematic significance. Biochem. Syst. Ecol. 2006, 34, 282–290. [Google Scholar] [CrossRef]
  91. Adesida, G.A.; Adesogan, E.K.; Okorie, D.A.; Taylor, D.A.H.; Styles, B.T. The limonoid chemistry of the genus Khaya (Meliaceae). Phytochemistry 1971, 10, 1845–1853. [Google Scholar] [CrossRef]
  92. Adesogan, E.K.; Taylor, D.A.H. Extractives from Khaya senegalensis (Desr.) A. Juss. J. Chem. Soc. C Org. 1968, 16, 790–791. [Google Scholar] [CrossRef]
  93. Luco, J.M.; Sosa, M.C.; Cesco, J.C.; Tonn, C.E.; Giordano, O.S. Molecular connectivity and hydrophobicity in the study of antifeedant activity of clerodane diterpenoids. Pestic. Sci. 1994, 41, 1–6. [Google Scholar] [CrossRef]
  94. Magrini, F.E.; Specht, A.; Gaio, J.; Girelli, C.P.; Migues, I.; Heinzen, H.; Saldana, J.; Sartori, V.C. Antifeedant activity and effects of fruits and seeds extracts of Cabralea canjerana canjerana (Vell.) Mart. (Meliaceae) on the immature stages of the fall armyworm Spodoptera frugiperda (JE Smith) (Lepidoptera: Noctuidae). Ind. Crops. Prod. 2015, 65, 150–158. [Google Scholar] [CrossRef]
  95. Alvarez, D.; Zuleta, D.; Saldamando, C.; Lobo-Echeverri, T. Selective activity of Carapa guianensis and Swietenia macrophylla (Meliaceae) against the corn and rice strains of Spodoptera frugiperda (Lepidoptera, Noctuidae). Int. J. Pest Manag. 2021. [Google Scholar] [CrossRef]
  96. Sarquis, I.R.; Sarquis, R.S.F.R.; Marinho, V.H.S.; Neves, F.B.; Araújo, I.F.; Damasceno, L.F.; Ferreira, R.M.A.; Souto, R.N.P.; Cavalho, I.C.T.; Ferreira, I.M. Carapa guianensis Aubl (Meliaceae) oil associated with silk fibroin, as alternative to traditional surfactants, and active against larvae of the vector Aedes aegypti. Ind. Crops. Prod. 2020, 157, 112931. [Google Scholar] [CrossRef]
  97. Isman, M.B.; Matsuura, H.; MacKinnon, S.; Durst, T.; Towers, G.H.N.; Arnason, J.T. Phytochemistry of the Meliaceae: So many terpenoids, so few insecticides. Phytochem. Redund. Ecol. Interact. 1996, 30, 155–178. [Google Scholar]
  98. Siddiqui, S.; Fuchs, S.; Lucke, J.; Voelter, W. Structure of a new natural compound in Melia azadirachta Linn. [Azadirachta indica]: 17-hydroxyazadiradion in the fruit. Tetrahedron Lett. 1978, 7, 611–612. [Google Scholar] [CrossRef]
  99. Kraus, W.; Cramer, R. 17-EPI-azadiradion uno 17-β-hydroxy-azadiradion, zwei neue inhaltsstoffe aus Azadirachta indica A. Juss. Tetrahedron Lett. 1978, 19, 2395–2398. [Google Scholar] [CrossRef]
  100. Nogueira, T.S.R.; Passos, M.S.; Nascimento, L.P.S.; Arantes, M.B.D.; Monteiro, N.O.; Boeno, S.I.D.; de Carvalho, A.; Azevedo, O.D.; Terra, W.D.; Vieira, M.G.C. Chemical Compounds and Biologic Activities: A Review of Cedrela Genus. Molecules 2020, 22, 5401. [Google Scholar] [CrossRef]
  101. Leo, M.D.; Milella, L.; Braca, A.; Tommasi, N.D. Cedrela and Toona genera: A rich source of bioactive limonoids and triterpenoids. Phytochem. Rev. 2018, 4, 751–783. [Google Scholar] [CrossRef]
  102. Chatterjee, A.; Chakrabortty, T.; Chandrasekharan, S. Chemical investigation of Cedrela toona. Phytochemistry 1971, 10, 2533–2535. [Google Scholar] [CrossRef]
  103. Leite, A.C.; Bueno, F.C.; Oliveira, C.G.; Fernandes, J.B.; Vieira, P.C.; Silva, M.F.G.F.; Bueno, O.C.; Pagnocca, F.C.; Hebling, M.J.A.; Bacci, M. Limonoids from Cipadessa fruticosa and Cedrela fissilis and their insecticidal activity. J. Brazil. Chem. Soc. 2005, 16, 1391–1395. [Google Scholar] [CrossRef] [Green Version]
  104. Green, M.B.; Hedin, P.A. Natural Resistance of Plants to Pests; American Chemical Society: Washington, DC, USA, 1986. [Google Scholar]
  105. Arnason, J.T.; Philogene, B.J.R.; Donskov, N.; Kubo, I. Limonoids from the Meliaceae and Rutaceae reduce feeding, growth and development of Ostrinia nubilalis. Entomol. Exp. Appl. 1987, 43, 221–226. [Google Scholar] [CrossRef]
  106. Bueno, F.C.; Godoy, M.P.; Leite, A.C.; Bueno, O.C.; Pagnocca, F.C.; Fernandes, J.B.; Hebling, M.J.A.; Bacci, M., Jr.; Vieira, P.C.; Silva, G.F. Toxicity of Cedrela fissilis to Atta Sexdens rubropilosa (Hymenoptera: Formicidae) and its symbiotic fungus. Sociobiology 2005, 45, 389–399. [Google Scholar]
  107. Laphookhieo, S.; Maneerat, W.; Koysomboon, S.; Kiattansakul, R.; Chantrapromma, K.; Syers, J.K. A novel limonoid from the seeds of Chisocheton siamensis. Can. J. Chem. 2008, 39, 205–208. [Google Scholar] [CrossRef]
  108. Connolly, J.D.; Labbe, C.; Rycroft, D.S.; Taylor, D.A.H. Tetranortriterpenoids and related compounds. Part 22. New apotirucailol derivatives and tetranortriterpenoids from the wood and seeds of Chisocheton paniculatus (Meliaceae). Chem. Soc. 1980, 11, 2959–2964. [Google Scholar] [CrossRef]
  109. Lavie, D.; Levy, E.C.; Jain, M.K. Limonoids of biogenetic interest from Melia azadirachta L. Tetrahedron 1971, 27, 3927–3939. [Google Scholar] [CrossRef]
  110. Luo, J.; Wang, J.S.; Wang, X.B.; Huang, X.F.; Luo, J.G.; Kong, L.Y. Chukvelutilides A–F, phragmalin limonoids from the stem barks of Chukrasia tabularis var. velutina. Tetrahedron 2009, 65, 3425–3431. [Google Scholar] [CrossRef]
  111. Fan, C.Q.; Wang, X.N.; Yin, S.; Zhang, C.R.; Wang, F.D.; Yue, J.M. Tabularisins A–D, phragmalin orthoesters with new skeleton isolated from the seeds of Chukrasia tabularis. Tetrahedron 2007, 63, 6741–6747. [Google Scholar] [CrossRef]
  112. Yin, J.L.; Fang, X.; Liu, E.D.; Yuan, C.M.; Li, S.F.; Zhang, Y.; He, H.P.; Li, S.L.; Di, Y.T.; Hao, X.J. Phragmalin limonoids from the stem barks of Chukrasia tabularis var. velutina. Planta Med. 2014, 80, 1304–1309. [Google Scholar] [CrossRef] [Green Version]
  113. Chen, X.L.; Liu, H.L.; Guo, Y.W. Phragmalin limonoids from Chukrasia tabularis var. velutina. Planta Med. 2012, 78, 286–290. [Google Scholar] [CrossRef]
  114. Truong, V.L.; Jeong, W.S. Cellular defensive mechanisms of tea polyphenols: Structure-activity relationship. Int. J. Mol. Sci. 2021, 17, 9109. [Google Scholar] [CrossRef] [PubMed]
  115. Kilani, M.S.; Morakchi, G.H.; Sifi, K. Azadirachtin-based insecticide: Overview, risk assessments, and future directions. Front. Agron. 2021, 3, 32. [Google Scholar] [CrossRef]
  116. Hein, D.F.; Hummel, H.E.; Ley, S.V. Structure activity relationships in azadirachtin a derivatives: Feeding activity and degree of efficiency tested on Epilachna varivestis larvae. Meded. Fac. Landbouwkd. En Toegep. Biol. Wet. Univ. Gent 1999, 64, 197–204. [Google Scholar]
  117. Lai, D.; Jin, X.; Wang, H.; Xu, H. Gene expression profile change and growth inhibition in Drosophila larvae treated with azadirachtin. J. Biotechnol. 2014, 185, 51–56. [Google Scholar] [CrossRef] [PubMed]
  118. Dawkar, V.V.; Barage, S.H.; Barbole, R.S.; Fatangare, A.; Grimalt, S.; Haldar, S.; Heckel, D.G.; Gupta, V.S.; Thulasiram, H.V.; Svatos, A. Azadirachtin-A from Azadirachta indica impacts multiple biological targets in cotton bollworm Helicoverpa armigera. ACS Omega 2019, 4, 9531–9541. [Google Scholar] [CrossRef] [PubMed]
  119. Lee, Y.; Kim, S.H.; Montell, C. Avoiding DEET through insect gustatory receptors. Neuron 2010, 67, 555–561. [Google Scholar] [CrossRef] [Green Version]
  120. Weiss, L.A.; Dahanukar, A.; Kwon, J.Y.; Banerjee, D.; Carlson, J.R. The molecular and cellular basis of bitter taste in Drosophila. Neuron 2011, 69, 258–272. [Google Scholar] [CrossRef] [Green Version]
  121. Delventhal, R.; Carlson, J.R. Bitter taste receptors confer diverse functions to neurons. eLife 2016, 5, 220. [Google Scholar] [CrossRef] [PubMed]
  122. Luntz, A.J.M.; Morgan, E.D.; Nisbet, A.J. Azadirachtin, a Natural Product in Insect Control. Compr. Mol. Insect Sci. 2005, 6, 117–135. [Google Scholar]
  123. Khosravi, R.; Sendi, J.J. Effect of neem pesticide (Achook) on midgut enzymatic activities and selected biological compounds in the hemolymph of lesser mulberry pyralid, Glyphodes pyloalis walker (Lepidoptera: Pyralidae). J. Plant Prot. Res. 2013, 53, 238–247. [Google Scholar] [CrossRef]
  124. Shannag, H.K.; Capinera, J.L.; Freihat, N.M. Effects of neem-based insecticides on consumption and utilization of food in larvae of Spodoptera eridania (Lepidoptera: Noctuidae). J. Insect Sci. 2015, 15, 152. [Google Scholar] [CrossRef] [Green Version]
  125. Yan, Y.; Gu, H.; Xu, H.; Zhang, Z. Induction of aversive taste memory by azadirachtin and its effects on dopaminergic neurons of Drosophila. J. South China Agric. Univ. 2017, 38, 12–18. [Google Scholar]
  126. Qiao, J.; Zou, X.; Lai, D.; Yan, Y.; Wang, Q.; Li, W.; Deng, S.; Xu, H.; Gu, H. Azadirachtin blocks the calcium channel and modulates the cholinergic miniature synaptic current in the central nervous system of Drosophila. Pest Manag. Sci. 2014, 70, 1041–1047. [Google Scholar] [CrossRef] [PubMed]
  127. Boulahbel, B.; Aribi, N.; Kilani, M.S.; Soltani, N. Insecticidal activity of azadirachtin on Drosophila melanogaster and recovery of normal status by exogenous 20-hydroxyecdysone. Afr. Entomol. 2015, 23, 224–233. [Google Scholar] [CrossRef]
  128. Oulhaci, M.C.; Denis, B.; Kilani, M.S.; Sandoz, J.C.; Kaiser, L.; Joly, D.; Aribi, N. Azadirachtin effects on mating success, gametic abnormalities and progeny survival in Drosophila melanogaster (Diptera). Pest Manag. Sci. 2018, 74, 174–180. [Google Scholar] [CrossRef] [PubMed]
  129. Vivekananthan, T.; Selvisabhanayakam, S.N. Histopathological observations on testes of adult blister beetle, Mylabris indica (thunberg) (Coleoptera: Meloidae) treated with neem. J. Entomol. Res. 2014, 38, 45–52. [Google Scholar]
  130. Ghazawi, N.A.; El-Shranoubi, E.D.; El-Shazly, M.M.; Abdel Rahman, K.M. Effects of azadirachtin on mortality rate and reproductive system of the grasshopper Heteracris littoralis Ramb (Orthoptera: Acrididae). J. Orthoptera Res. 2007, 16, 57–65. [Google Scholar] [CrossRef] [Green Version]
  131. Aribi, N.; Oulhaci, M.C.; Kilani, M.S.; Sandoz, J.C.; Kaiser, L.; Denis, B.; Joly, D. Azadirachtin impact on mate choice, female sexual receptivity and male activity in Drosophila melanogaster (Diptera: Drosophilidae). Pestic. Biochem. Physiol. 2017, 143, 95–101. [Google Scholar] [CrossRef]
  132. Liu, P.F.; Wang, W.; Ling, X.; Lu, Q.; Zhang, J.; He, R.; Chen, H. Regulation hormone-related genes in Ericerus pela (Hemiptera: Coccidae) for dimorphic metamorphosis. J. Insect Sci. 2019, 19, 16–25. [Google Scholar]
  133. Zhao, J.; Zhou, Y.; Li, X.; Cai, W.; Hua, H. Silencing of juvenile hormone epoxide hydrolase gene (Nljheh) enhances short wing formation in a macropterous strain of the brown planthopper, Nilaparvata lugens. J. Insect Physiol. 2017, 102, 18–26. [Google Scholar] [CrossRef]
  134. Shu, B.; Wang, W.; Hu, Q.; Huang, J.; Hu, M.; Zhong, G. A comprehensive study on apoptosis induction by azadirachtin in Spodoptera frugiperda cultured cell line Sf9. Arch. Insect Biochem. Physiol. 2015, 89, 153–168. [Google Scholar] [CrossRef]
  135. Roberston, S.L.; Ni, W.; Dhadialla, T.S.; Nisbet, A.J.; McCusker, C.; Ley, S.V.; Mordue, W. Identification of a putative azadirachtin-binding complex from Drosophila Kc167 cells. Arch. Insect Biochem. Physiol. 2007, 64, 200–208. [Google Scholar]
Ijms 22 13262 g001 550
Figure 1. The structural classification of triterpenes.
Figure 1. The structural classification of triterpenes.
Ijms 22 13262 g001
Ijms 22 13262 g002a 550Ijms 22 13262 g002b 550
Figure 2. The 19 insecticidal plant species from genera Aglaia, Aphanamixis, Azadirachta, Carapa, Cedrela, Cabralea, Chisocheton, and Chukrasia in Meliaceae.
Figure 2. The 19 insecticidal plant species from genera Aglaia, Aphanamixis, Azadirachta, Carapa, Cedrela, Cabralea, Chisocheton, and Chukrasia in Meliaceae.
Ijms 22 13262 g002aIjms 22 13262 g002b
Ijms 22 13262 g003a 550Ijms 22 13262 g003b 550
Figure 3. The structures of ring intact limonoids: azadirones.
Figure 3. The structures of ring intact limonoids: azadirones.
Ijms 22 13262 g003aIjms 22 13262 g003b
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Figure 4. The structure of ring intact limonoids: cedrelone, azadiraindin A, and meliatetraolenone.
Figure 4. The structure of ring intact limonoids: cedrelone, azadiraindin A, and meliatetraolenone.
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Ijms 22 13262 g005a 550Ijms 22 13262 g005b 550
Figure 5. The structures of ring A-seco chemicals.
Figure 5. The structures of ring A-seco chemicals.
Ijms 22 13262 g005aIjms 22 13262 g005b
Ijms 22 13262 g006 550
Figure 6. The structures of azadirachtin/meliacarpin-class chemicals.
Figure 6. The structures of azadirachtin/meliacarpin-class chemicals.
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Ijms 22 13262 g007 550
Figure 7. The structures of salannin-class chemicals.
Figure 7. The structures of salannin-class chemicals.
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Ijms 22 13262 g008 550
Figure 8. The structures of nimbin-class chemical: 6-deacetylnimbin.
Figure 8. The structures of nimbin-class chemical: 6-deacetylnimbin.
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Ijms 22 13262 g009a 550Ijms 22 13262 g009b 550
Figure 9. The structures of ring D-seco chemicals.
Figure 9. The structures of ring D-seco chemicals.
Ijms 22 13262 g009aIjms 22 13262 g009b
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Figure 10. The structures of rings A,B-seco chemicals: prieurianins.
Figure 10. The structures of rings A,B-seco chemicals: prieurianins.
Ijms 22 13262 g010
Ijms 22 13262 g011a 550Ijms 22 13262 g011b 550
Figure 11. The structures of rings A,B-seco chemicals: aphanamixoids.
Figure 11. The structures of rings A,B-seco chemicals: aphanamixoids.
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Figure 12. The structures of A,D-seco chemicals.
Figure 12. The structures of A,D-seco chemicals.
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Ijms 22 13262 g013 550
Figure 13. The structures of B,D-seco chemicals.
Figure 13. The structures of B,D-seco chemicals.
Ijms 22 13262 g013
Ijms 22 13262 g014a 550Ijms 22 13262 g014b 550
Figure 14. The structures of mexicanolides.
Figure 14. The structures of mexicanolides.
Ijms 22 13262 g014aIjms 22 13262 g014b
Ijms 22 13262 g015 550
Figure 15. The structures of phragmalins.
Figure 15. The structures of phragmalins.
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Figure 16. The structure of 10,11-linkage group chemical: cipadesin B.
Figure 16. The structure of 10,11-linkage group chemical: cipadesin B.
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Ijms 22 13262 g017 550
Figure 17. The structures of pentanortriterpenoids.
Figure 17. The structures of pentanortriterpenoids.
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Figure 18. The structures of octanortriterpenoids.
Figure 18. The structures of octanortriterpenoids.
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Ijms 22 13262 g019 550
Figure 19. The structures of dammaranes.
Figure 19. The structures of dammaranes.
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Figure 20. The structures of protolimonoids.
Figure 20. The structures of protolimonoids.
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Figure 21. The structures of oleananes.
Figure 21. The structures of oleananes.
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Table
Table 1. The 19 insecticidal plant species of 8 genera in Meliaceae.
Table 1. The 19 insecticidal plant species of 8 genera in Meliaceae.
FamilyGenusSpecies
MeliaceaeAglaiaAglaia elaeagnoidea (A. Juss.) Benth.
AphanamixisAphanamixis grandifolia Bl.
Aphanamixis polystachya (Wall.) R. Parker
AzadirachtaAzadirachta excelsa (Jack) Jacobs
Azadirachta indica A. Juss
Azadirachta siamensis Val.
CabraleaCabralea canjerana (Vell.) Mart
CarapaCarapa guianensis Aubl.
CedrelaCedrela dugessi (S. Watson)
Cedrela fissilis Vell.
Cedrela odorata L.
Cedrela salvadorensis L.
Cedrela sinensis Juss.
Cedrela toona Roxb. Ex Rottler et Willd.
Chisocheton ceramicus (Miq.) C.DC.
ChisochetonChisocheton paniculatus (Roxb.) Hiern
Chisocheton siamensis Craib
Chisocheton erythrocarpus Hiern
ChukrasiaChukrasia tabularis A. Juss.
Table
Table 2. Antifeedant activity of insecticidal triterpenoids of plants from 8 genera in Meliaceae.
Table 2. Antifeedant activity of insecticidal triterpenoids of plants from 8 genera in Meliaceae.
CompoundPlant SourceInsectActivityRef.
Aphanamixoid AAphanamixis polystachyaHelicoverpa armigeraAFD *, EC50 = 0.015 μmol/cm2 (24 h)[31]
Aphanamixoid CAphanamixis polystachyaHelicoverpa armigeraAFD, EC50 = 0.017 μmol/cm2 (24 h)[18]
Aphanamixoid FAphanamixis polystachyaHelicoverpa armigeraAFD, EC50 = 0.008 μmol/cm2 (24 h)
Aphanamixoid GAphanamixis polystachyaHelicoverpa armigeraAFD, EC50 = 0.012 μmol/cm2 (24 h)
PrieurianinAphanamixis polystachyaHelicoverpa armigeraAFD, EC50 = 18.8 μg/mL (7 d)[34]
EpoxyprieurianinAphanamixis polystachyaHelicoverpa armigeraAFD, EC50 = 3.2 μg/mL (7 d)[34]
AzadirachtinAzadirachta indica
Azadirachta excelsa		Epilachna varivestiAFD, EC50 = 13 μg/mL (24 h)[9,10,11,12,13,15,16,33,35,36]
Epilachna paenulataAFD, LD50 = 1.24 μg/cm2 (96 h)
Helicoverpa armigeraAFD, EC50 = 0.26 μg/mL (6 h)
Locusta migratoriaAFD, MIC = 25 μg/mL
Locusta migratoriaAFD, ED50 = 3 μg/mL (48 h)
Ostrinia nubilalisAFD, PC50 = 3.5 μg/mL (48 h)
Peridroma sauciaAFD, EC50 = 0.26 μg/mL (72 h)
Pieris rapaeAFD, AR = 100(1000 μg/mL) (24 h)
Phyllotreta striolataAFD, MIC = 10 μg/mL
Reticulitermes speratusAFD, PC95 = 65.293 (25 d)
Rhodnius prolixusAFD, ED50 = 25.0 μg/mL (25 d)
Schistocerca gregariaAFD, ED50 = 0.001 μg/mL
Spodoptera littoralisAFD, AI = 98.8 ± 1.11 (1 μg/mL) (8 h)
AzadironeAzadirachta indicaLeptinotarsa decemlineataAI = 11.6–26.9(100–500 μg/mL) (20 h)[37]
7-deacetylgeduninAzadirachta indicaReticulitermes speratusAFD, PC95 = 113.7 μg/disc (30 d)[23]
Cedrela fissilis
Cedrela sinensis
Chisocheton compound FChisocheton paniculatusPieris brassicaeAntifeedant activity [38]
SalanninAzadirachta indicaReticulitermes speratusAFD, PC95 = 203.3 μg/disc (30 d)[23]
Spodoptera lituraFRA50 # = 2.8 µg/cm2 (7 d)[22]
GeduninAzadirachta indicaReticulitermes speratusAFD, PC95 = 218.4 μg/disc (30 d)[23]
Cedrela dugessi
Cedrela fissilis
Cedrela sinensis
Cedrela salvadorensis
Cabralea eichleriana
Carapa guianensis
Chisocheton paniculatus
17β-hydroxy-
azadiradione		Azadirachta indicaReticulitermes speratusAFD, PC95 = 235.6 μg/disc (30 d)[23]
Carapa guianensis
nimbandiolAzadirachta indicaReticulitermes speratusAFD, PC95 = 254.4 μg/disc (30 d)[23]
3-deacetylsalanninAzadirachta indicaReticulitermes speratusAFD, PC95 = 1373.1 μg/disc (30 d)[23]
6-deacetylnimbinAzadirachta indicaReticulitermes speratusAFD, PC95 = 1581.2 μg/disc (30 d)[23]
Azadirachtin BAzadirachta indicaLocusta migratoriaAFD, EC50 = 12 μg/mL[39]
Azadirachta excelsaEpilachna varivestiAFD, EC50 = 30 μg/mL[9]
NimbolideAzadirachta indicaEpilachna varivestiAFD, EC50 = 90 μg/mL[9]
Azadirachta excelsa
Azadirachtin LAzadirachta indicaEpilachna varivestiAFD, EC50 = 6 μg/mL[9]
Azadirachta excelsa
1-tigloyl-3-acetyl-
azadirachtol		Azadirachta excelsaEpilachna varivestiAFD, EC50 = 6 μg/mL[9]
Azadirachta siamensis
SalannolAzadirachta indicaSpodoptera lituraFRA50 = 2.3 µg/cm2 (7 d)[22]
Azadiraindin AAzadirachta indicaPlutella xylostellaAR = 28% at 2000 μg/mL (48 h)[24]
EpoxyazadiradioneAzadirachta indicaPlutella xylostellaAR = 37.2% at 2000 μg/mL (48 h)[24]
DesfuranoazadiradioneAzadirachta indicaPlutella xylostellaAR = 39.6% at 2000 μg/mL (48 h)[24]
AzadiradioneAzadirachta indicaPlutella xylostellaAR = 90.6% at 2000 μg/mL (48 h)[24]
Chisocheton siamensis
7-deacetoxy-7-oxo-
gedunin		Cedrela fissilisSpodoptera littoralisAFD at 1000 μg/mL (3–10 h)[20]
Cabralea eichleriana
Carapa guianensis
Methyl angolensateCedrela fissilisSpodoptera lituraAFD, PFI = 65.3 at 1 μg/cm2 (24 h)[40]
Cabralea canjerana
11β-acetoxyobacunyl acetateCedrela odorataSpodoptera littoralisAFD at 1000 μg/mL[29]
11β,19-diacetoxy-l-de-
acetyl-l-epidihy-
dronomilin		Cedrela odorataSpodoptera littoralisAFD at 1000 μg/mL[29]
11β-acetoxyobacunolCedrela odorataSpodoptera littoralisAFD at 1000 μg/mL[29]
OdoralideCedrela odorataSpodoptera littoralisAFD at 1000 μg/mL[29]
SwietenolideCedrela odorataSpodoptera littoralisAFD at 1000 μg/mL[29]
8β,14α-dihydro-
swietenolide		Cedrela odorataSpodoptera littoralisAFD at 500 μg/mL[29]
3β,6-dihydroxydihydro
-carapin		Cedrela odorataSpodoptera littoralisAFD at 1000 μg/mL[29]
3β-hydroxydihydro-
carapin		Cedrela odorataSpodoptera littoralisAFD at 1000 μg/mL[29]
Xyloccensin KCedrela odorataSpodoptera littoralisAFD at 1000 μg/mL[29]
CedrodorinCedrela odorataSpodoptera littoralisAFD at 1000 μg/mL[29]
OcotilloneCabralea canjeranaSpodoptera lituraAFD, PFI = 44.5 at 1 μg/cm2 (24)[41]
TabulalinChukrasia tabularisSpodoptera littoralisAFD at 500 μg/mL (2–12 h)[42]
Tabulalide DChukrasia tabularisSpodoptera littoralisAFD at 500 μg/mL (2–12 h)[42]
TabulalideAChukrasia tabularisSpodoptera littoralisAFD at 1000 μg/mL (2–12 h)[42]
Tabulalide BChukrasia tabularisSpodoptera littoralisAFD at 1000 μg/mL (2–12 h)[42]
Tabulalide EChukrasia tabularisSpodoptera littoralisAFD at 1000 μg/mL (2–12 h)[42]
*: AFD means antifeedant activity; #: FRA50 means feeding reducing activity by 50%.
Table
Table 3. Poisonous activity of insecticidal triterpenoids of plants from 8 genera in Meliaceae.
Table 3. Poisonous activity of insecticidal triterpenoids of plants from 8 genera in Meliaceae.
CompoundPlant SourceInsectActivityRef.
Aphapolynin DAphanamixis polystachyaDiabrotica balteataMS: 66 5–9 d)[19]
Aphanalide FAphanamixis polystachyaDiabrotica balteataMS: 66 (5–9 d)
Aphapolynin FAphanamixis polystachyaDiabrotica balteataMS: 33 (5–9 d)
Dregenana-1Aphanamixis polystachyaDiabrotica balteataMS: 33 (5–9 d)
Aphanalide EAphanamixis polystachyaDiabrotica balteataMS: 33 (5–9 d)
Aphanalide GAphanamixis polystachyaDiabrotica balteataMS: 33 (5–9 d)
Aphanalide HAphanamixis polystachyaDiabrotica balteataMS: 99 (5–9 d)
Aphapolynin CAphanamixis polystachyaDiabrotica balteataMS: 99 (5–9 d)
Aphanamixis polystachyaCaenorhabditis elegansMS: 66 (5–9 d)
Aphapolynin AAphanamixis polystachyaPlutella xylostellaMS: 66 (5–9 d)
Zaphaprinin I Aphanamixis polystachyaPlutella xylostellaMS: 99 (5–9 d)
Zaphaprinin RAphanamixis polystachyaPlutella xylostellaMS: 99 (5–9 d)
AzadirachtinAzadirachta indica Azadirachta excelsaSpodoptera littoralisLC50 = 0.32 μg/mL (12 d)[9,10,11,12,13,15,16,33,35,36]
Anopheles gambiaeLD50 = 57.1 μg/mL (24 h)
Plutella xylostellaLD50 = 7.04–0.87 (24–96 h)
7-deacetylgeduninAzadirachta indicaAtta sexdens rubropilosaS50 = 9 d at 100 μg/mL[28]
Cedrela fissilis
Cedrela sinensis
GeduninAzadirachta indicaSpodoptera frugiperdaLC50 = 39 μg/mL (7 d)[43]
Cedrela dugessi
Cedrela fissilis
Cedrela sinensis
Cedrela salvadorensis
Cabralea eichleriana
Carapa guianensis
Chisocheton paniculatus
NimocinolAzadirachta indicaAedes aegyptiLC50 = 21 μg/mL (24 h)[25]
6α-O-acetyl-7-deacetyl-
nimocinol		Azadirachta indicaAedes aegyptiLC50 = 83 μg/mL (24 h)[25]
22,23-dihydronimocinolAzadirachta indicaAnopheles stephensiLC50 = 60 μg/mL (24 h)[26]
desfurano-6α-hydroxy-
azadiradione		Azadirachta indicaAnopheles stephensiLC50 = 43 μg/mL (24 h)[26]
MeliatetraolenoneAzadirachta indicaAnopheles stephensiLC50 = 16 μg/mL (24 h)[26]
OdoratoneAzadirachta indicaAnopheles stephensiLC50 = 154 μg/mL (24 h)[44]
Azadirachtin OAzadirachta excelsaPlutella xylostellaLD50 = 3.92 μg/g (24 h)[33]
Azadirachtin PAzadirachta excelsaPlutella xylostellaLD50 = 2.19 μg/g (24 h)[33]
Azadirachtin QAzadirachta excelsaPlutella xylostellaLD50 = 1.10 μg/g (96 h)[33]
Azadirachtin BAzadirachta excelsaPlutella xylostellaLD50 = 1.06 μg/g (96 h)[33]
Azadirachtin LAzadirachta excelsaPlutella xylostellaLD50 = 1.92 μg/g (96 h)[33]
Azadirachtin MAzadirachta excelsaPlutella xylostellaLD50 = 1.30 μg/g (96 h)[33]
11α-azadirachtin HAzadirachta excelsaPlutella xylostellaLD50 = 0.75 μg/g (96 h)[33]
AzadirachtolAzadirachta excelsaPlutella xylostellaLD50 = 1.78 μg/g (96 h)[33]
23-O-methylnimocinolideAzadirachta indicaAedes aegyptiLC50 = 53 μg/mL (24 h)[45]
7-O-deacetyl-23-O-methyl-
7α-O-senecioyl-nimocinolide		Azadirachta indicaAedes aegyptiLC50 = 14 μg/mL (24 h)[45]
6α-acetoxygeduninAglaia elaeagnoideaAtta sexdens rubropilosaS50 = 8 d at 100 μg/mL[28]
Carapa guianensis
Cedrela fissilis
Chisochetonpaniculatus
14-deoxy-Δ14,15-xyloccensin K Chisocheton erythrocarpus HiernAedes aegypti,
Aedes albopictus
Culex Quinquefasciatus		LC50 = 10.2 μg/mL (24 h) LC50 = 12.16 μg/mL (24 h) LC50 = 16.82 μg/mL (24 h)[46]
14-deoxyxyloccensin KChisocheton erythrocarpus Hiern
Chisocheton ceramicus		Aedes aegypti,
Aedes albopictus
Culex Quinquefasciatus		LC50 = 3.19 μg/mL (24 h)
LC50 = 3.01 μg/mL (24 h) LC50 = 3.64 μg/mL (24 h) 		[46]
Photogedunin epimer mixtureCedrela dugessiSpodoptera frugiperdaLC50 = 10 μg/mL (7 d)[47]
Photoacetic acid acetate mixtureCedrela dugessiSpodoptera frugiperdaLC50 = 8 μg/mL (7 d)[47]
7-deacetoxy-7-oxo-geduninCedrela fissilisAtta sexdens rubropilosaS50 = 11 d at 100 μg/mL[28]
Cabralea eichleriana
Carapa guianensis
PhotogeduninCedrela fissilisAtta sexdens rubropilosaS50 = 9 d at 100 μg/mL[28]
1,2-dihydro-3β-hydroxy-7-
deacetoxy-7-oxogedunin		Cedrela fissilisAtta sexdens rubropilosaS50 = 9 d at 100 μg/mL
Cipadesin BCedrela fissilisAtta sexdens rubropilosaS50 = 9 d at 100 μg/mL[28]
SwietemahonolideCedrela fissilisAtta sexdens rubropilosaS50 = 8 d at 100 μg/mL
3β-acetoxycarapinCedrela fissilisAtta sexdens rubropilosaS50 = 8 d at 100 μg/mL
Oleanolic acidCedrela fissilisAtta sexdens rubropilosaS50 = 6 d at 100 μg/mL
Oleanonic acidCedrela fissilisAtta sexdens rubropilosaS50 = 8 d at 100 μg/mL
Methyl angolensateCedrela fissilisSpodoptera frugiperdaMR: 40% at 50 mg/kg (7 d)[48]
Cabralea canjerana
Photogeduninepimeric acetate mixtureCedrela salvadorensisSpodoptera frugiperdaSR 50% at 10 μg/mL (24 h)[49]
Photogeduninepimeric mixtureCedrela salvadorensisSpodoptera frugiperdaSR 17% at 10 μg/mL (24 h)
OcotilloneCabralea canjeranaSpodoptera frugiperdaMR: 40% at 50 mg/kg (7 d)[48]
β-photogeduninCarapa guianensisSpodoptera frugiperdaLM 53.3% at 50 μg/mL (7 d)[48]
PM 20.0% at 50 μg/mL (7 d)
MS: mortality scored; SR: survival rate; MR: mortality rate; LM: larval mortality; PM: pupal mortality.
Table
Table 4. Growth regulatory activity of insecticidal triterpenoids of plants from 8 genera in Meliaceae.
Table 4. Growth regulatory activity of insecticidal triterpenoids of plants from 8 genera in Meliaceae.
CompoundPlant SourceInsectActivityRef.
AzadirachtinAzadirachta indica
Azadirachta excelsa		Helicoverpa armigeraIGR, EC50 = 0.26 μg/mL (7 d)[9,10,11,12,13,15,16,33,35,36]
Rhodnius prolixusIGR, ED50 = 0.40 μg/mL (7 d)
Heliothis zea
Heliothis virescens		IGR, ED50 = 0.70 μg/mL (10 d)
Spodoptera frugiperda,
Pectinophora gossypiella		IGR, ED50 = 0.40 μg/mL (10 d)
Spodoptera lituraIGR, EC50 = 0.21 μg/mL (7 d)
Spodoptera littoralisEC50 = 0.11 μg/mL (6 d)
NimocinolideAzadirachta indicaMusca domesticaFI at 100 μg/mL[27]
IsonimocinolideAzadirachta indicaMusca domesticaFI at 100 μg/mL[27]
Aedes uegyptimutagenic properties
7-deacetylazadiradioneAzadirachta indicaHeliothis virescensIGR, EC50 = 1600 μg/mL[30]
Chisocheton paniculatus
SalanninAzadirachta indicaHelicoverpa armigeraIGR EC50 = 86.5 μg/mL (7 d)[22]
Azadirachta indicaSpodoptera lituraIGR EC50 = 87.7 μg/mL (7 d)
3-O-acetyl salannolAzadirachta indicaHelicoverpa armigeraIGR EC50 = 64.2 μg/mL (7 d)[22]
Azadirachta indicaSpodoptera lituraIGR EC50 = 65.6 μg/mL; RF50 at 2.0 µg/cm2 (7 d)
SalannolAzadirachta indicaHelicoverpa armigeraIGR, EC50 was 79.7 μg/mL (7 d)[22]
Azadirachta indicaSpodoptera lituraIGR, EC50 = 77.4 μg/mL (7 d)
6β-hydroxygeduninAzadirachta indicaHelicoverpa armigeraIGR EC50 = 24.2 μg/mL (7 d)[35]
Azadirachta indicaSpodoptera lituraIGR EC50= 391.4 μg/mL (7 d)
NimbineneAzadirachta indicaHelicoverpa armigeraIGR EC50 was 21.5 μg/mL (7 d)[35]
Azadirachta indicaSpodoptera lituraIGR EC50 = 404.5 μg/mL (7 d)
AzadiradioneAzadirachta indicaHeliothis virescensIGR, EC50= 560 μg/mL[30]
Chisocheton siamensis
Azadirachta indicaHeliothis virescensIGR, EC50 = 560 μg/mL[30]
Chisocheton siamensis
6α-acetoxygeduninAglaia elaeagnoideaOstrinia nubilalisreduced growth at 50 μg/mL[17]
Carapa guianensis
Cedrela fissilis
Chisocheton paniculatus
Cedrelanolide I Cedrela salvadorensisOstrinia nubilalisreduced weight at 50 μg/mL[51]
CedreloneCedrela odorataPeridroma sauciaIGR, EC50 = 53.1 μg/mL (9 d)[29]
Cedrela toona
CabraleadiolCabralea canjeranaSpodoptera frugiperdaLPE, 1.2 d[48]
3β-deacetylfissinolideCabralea canjeranaSpodoptera frugiperdaLPE, 1.2 d[48]
β-photogeduninCarapa guianensisSpodoptera frugiperdaPWI at 50 mg/kg (7 d)[48]
Cedrelanolide I Cedrela salvadorensisOstrinia nubilalisreduced weight at 50 μg/mL[51]
MeliantriolAzadirachta indicaLocustschewing prevention[52]
7-deacetyl-17β-hydroxy-azadiradioneAzadirachta indicaHeliothis virescensIGR, EC50 = 240 μg/mL[30]
IGR: insect growth inhibitory activity; LPE: larval phase extended; FI: fecundity inhibition; RF50: reduced feeding by 50%; PWI: pupal weight inhibition.
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Lin, M.; Yang, S.; Huang, J.; Zhou, L. Insecticidal Triterpenes in Meliaceae: Plant Species, Molecules and Activities: Part Ⅰ (Aphanamixis-Chukrasia). Int. J. Mol. Sci. 2021, 22, 13262. https://doi.org/10.3390/ijms222413262

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Lin M, Yang S, Huang J, Zhou L. Insecticidal Triterpenes in Meliaceae: Plant Species, Molecules and Activities: Part Ⅰ (Aphanamixis-Chukrasia). International Journal of Molecular Sciences. 2021; 22(24):13262. https://doi.org/10.3390/ijms222413262

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Lin, Meihong, Sifan Yang, Jiguang Huang, and Lijuan Zhou. 2021. "Insecticidal Triterpenes in Meliaceae: Plant Species, Molecules and Activities: Part Ⅰ (Aphanamixis-Chukrasia)" International Journal of Molecular Sciences 22, no. 24: 13262. https://doi.org/10.3390/ijms222413262

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