Potential Insect Growth Regulator Research Articles

Design, Synthesis, and Biological Activity of Novel Benzo[d][1,3]dioxole-6-benzamide Derivatives: Multichitinase Inhibitors as Potential Insect Growth Regulator Candidates.

Insect growth regulators (IGRs) disrupt normal development of physiological processes in insects and are recognized as green insecticides. Insect chitinases play a crucial role in cuticle degradation during molting, and OfChtI, OfChtII, and OfChi-h are the prospective targets for discovering new insecticides as IGRs. In our previous study, we identified the lead compound a12 as a promising multitarget inhibitor. Herein, we used the binding modes of a12 with three chitinases to recognize the critical interactions and residues favorable to the bioactivity. Subsequently, to improve the bioactivity of inhibitors via enhanced the interactions with important residues, a series of benzo[d][1,3]dioxole-6-benzamide derivatives were rationally designed and synthesized, and their inhibitory activities against Ostrinia furnacalis (O. furnacalis) chitinases, as well as insecticidal activities against O. furnacalis and Plutella xylostella (P. xylostella) were investigated. Among them, compound d29 acted simultaneously on OfChtI, OfChtII, and OfChi-h with Ki values of 0.8, 11.9, and 2.3 μM, respectively, a significant improvement over the inhibitory activity of the lead compound a12. Moreover, d29 exhibited superior activity than a12 against two lepidopteran pests by interfering with normal insect growth and molting, indicating that d29 is a potential lead candidate for novel IGRs with a multichitinase mechanism. The present study revealed that simultaneous inhibition on multiple chitinases could achieve excellent insecticidal activity. The elucidation of inhibition mechanisms and molecular conformations illustrated the interactions with the three chitinases, as well as the discrepancy in bioactivity, which will be beneficial for future work to improve the potency of bioactivity as IGRs for pest control in sustainable agriculture.

Synthesis, structural, DFT and bio-assay of novel ethyl 3-(2-(4-chlorophenoxy)acetamido) propanoate on Galleria mellonela (wax moth) – a juvenile hormone mimic as potential insect growth regulator (IGR)

Ethyl 3-(2-(4-chlorophenoxy)acetamido)propanoate is synthesized and comprehensively studied as an insect growth regulator. The structure has been confirmed using fourier transform infra-red (FT-IR), nuclear magnetic resonance (1D-NMR, 2D-NMR), electrospray ionization (ESI-MS) spectroscopic techniques. The synthesized compound has been tested against the fifth instar of Galleria mellonella in comparison to pyriproxyfen (commercial IGR). Observed LC50 and LC90 values of synthesized compound and pyriproxyfen are 162 ppm & 549 ppm and 125 & 630 ppm respectively. Computational and structural parameters of the synthesized compound are determined and studied. Molecular geometry and unscaled vibrational frequencies are calculated by density functional theory (DFT) method using Becke's three-parameter lee-yang-parr (B3LYP) hybrid functional at 6–311G+(d,2p) level of basis set. The scaled quantum mechanical (SQM) method has been employed to calculate scaled vibrational frequencies. Further, 1H and 13C NMR spectra are calculated with (DFT/ B3LYP) using gage independent atomic orbital method (GIAO) in the gaseous and solvent phases to confirm the structure of synthesized compound. Natural bond orbital (NBO) analysis has been used to study the intramolecular charge transfer (ICT) interactions, delocalization of electron density. HOMO-LUMO energies are calculated to describe global reactivity descriptors which played an important role in explaining the bioactivity of compounds. Parameters are also evaluated in solvent phases using the integral equation formalism polarization continuum model (IEF-PCM) of the DFT method. The Autodock software tool is used to study the binding interactions between ligand and receptor juvenile hormone binding protein (JHBP).

A steroidal lactone, withaferin A acts as a potential insect growth regulator against polyphagous pest, Spodoptera litura (Lepidoptera: Noctuidae)

Administration of a steroidal lactone, withaferin A to last larval instar of a polyphagous pest, Spodoptera litura caused severe impairment of development resulting into a significant delay in larval–pupal and pupal–adult ecdysis, larval mortality, ecdysial stasis, formation of larval–pupal and pupal–adult intermediates, suppression of pupation and adult emergence and formation of abnormal pupae and adultoids. The LC50 value in topical administration of withaferin A was 180.3 µg·µL−1 against freshly moulted sixth instar larvae of S. litura. This suggests that a bioactive ingredient withaferin A, found in the parts of the medicinal plant, Withania somnifera interferes with the neuroendocrine system of the insects resulting into disruption of moulting and metamorphosis. The active ingredient, withaferin A from W. somnifera may be safely and judiciously employed for the control of S. litura under field conditions along with other bio-rational approaches for insect pest management programs.

Design, Synthesis, and Biological Activity of Novel Heptacyclic Pyrazolamide Derivatives: A New Candidate of Dual-Target Insect Growth Regulators.

Insect growth regulators (IGRs) can cause abnormal growth and development in insects, resulting in incomplete metamorphosis or even death of the larvae. Ecdysone receptor (EcR) and chitinase in insects play indispensable roles in the molting process. Ecdysone analogues and chitinase inhibitors are considered as potential IGRs. In order to find new and highly effective IGR candidates, based on the structure-activity relationship and molecular docking results of the active compound 6i (3-(tert-butyl)-N-(4-(tert-butyl)phenyl)-1-phenyl-1H-pyrazole-5-carboxamide) discovered in our previous work, we changed the t-butyl group on the pyrazole ring into heptacycle to enhance the hydrophobicity. Consequently, a series of novel heptacyclic pyrazolamide derivatives were designed and synthesized. The bioassay results demonstrated that some compounds showed obvious insecticidal activity. Especially, D-27 (N-(4-(tert-butyl)phenyl)-2-phenyl-2,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-5-carboxamide) showed good activities against Plutella xylostella (LC50, 51.50 mg·L-1) and Mythimna separata (100% mortality at 2.5 mg·L-1). Furthermore, protein validation indicated that D-27 acts not only on the EcR but also on chitinase Of ChtI. Molecular docking and molecular dynamics simulation explained the vital factors in the interaction between D-27 and receptors. D-27 may be a new lead candidate with a dual target in which Of ChtI shall be the main one. This work created a new starting point for discovering a novel type of IGRs.

Cucurbitacin B acts a potential insect growth regulator by antagonizing 20-hydroxyecdysone activity.

20-Hydroxyecdysone (20E), a crucial insect steroid hormone, can bind to its cognate nuclear receptor composed of ecdysone receptor (EcR) and ultraspiracle (USP) to activate expression of 20E-response genes, enabling subsequent metamorphosis. In this study, we tried to find out which steroid-like compounds can block insect metamorphosis effectively and provide useful information for biopesticide study. For this purpose, we screened 126 steroid-like compounds for possible 20E antagonists using a dual-luciferase reporter assay with Drosophila melanogaster Kc and Bombyx mori Bm12 cells. Among 126 steroid-like compounds, three cucurbitacins (CucB, D and E) were identified as 20E antagonists in both Kc and Bm12 cells. Notably, CucB caused significant molting defects and mortality in both B. mori and D. melanogaster larvae, and dramatically hindered larval growth of Helicoverpa armigera by its anti-feeding activity. In vivo and in vitro experiments demonstrate that CucB acts as a potential insect growth regulator by antagonizing 20E activity and thus blocking molting and metamorphosis induced by 20E signaling. © 2017 Society of Chemical Industry.

Withania somnifera acts as a potential insect growth regulator in the polyphagous pest, Pericallia ricini

Abstract Both seed and root extracts of the medicinal plant, Ashwagandha, Withania somnifera exhibit insect growth regulatory activity against the polyphagous pest, Pericallia ricini. Topical administration of W. somnifera seed and root extracts to last instar larvae of P. ricini disrupted moulting and metamorphosis, leading to a number of developmental abnormalities such as delay in larval-pupal and pupal-adult ecdysis, formation of larval-pupal, pupal-adult and larval-pupal-adult mosaics/chimeras, ecdysial failure, suppression of pupation and adult emergence and formation of abnormal pupae and adultoids. The treatment with seed extracts was more severe than that of root extracts as it completely suppressed the pupation and adult emergence. The results clearly suggest that the medicinal plant, W. somnifera acts as a potential insect growth regulatory (IGR) disrupting the moulting and metamorphosis as a consequence of interference with the endocrine system.

A potential insect growth regulator forcockroach control: design, synthesis andbioactivity of N-terminal-modified allatostatin analogues.

The FGLa-allatostatins (ASTs) are a family of neuropeptides that can inhibit juvenile hormone biosynthesis by the corpora allata (CA) in vitro, and therefore they are regarded as insect growth regulator (IGR) candidates for pest control. In our previous studies, an AST mimic, H17, was found to have a significant effect on JH biosynthesis by cockroach CA, both invitro and in vivo. To discover new potential mimics and explore the substituent effect on the inhibition of JH biosynthesis, 30 analogues, modified with various substituents on the benzene ring at the N-terminus of lead compound H17, were designed and synthesised. Their bioactivity in inhibiting JH biosynthesis by the CA of Diploptera punctata and the potency of M9, M10 and M11 in activation of Dippu-AstR were evaluated. All the analogues showed an effect on JH biosynthesis by CA in vitro. M9, M10 and M11 can activate the Dippu-AstR, albeit with much lower potency than that of AST 1. M11 also exhibited improved in vitro activity (IC50 6.98 nm) in comparison with the lead compound H17 (IC50 29.5 nm). In particular, M11 displayed good in vivo activity in inhibiting JH biosynthesis and basal oocyte growth. The structure-activity relationship studies suggest that different positions of substituents on the benzene ring of the cinnamic acid can lead to different activities. The para-substitution on the benzene ring plays an important role in inhibiting JH biosynthesis in vitro. Moreover, M11 is considered to be a potential IGR for cockroach control. © 2016 Society of Chemical Industry.

Synthesis and biological activity of FGLamide allatostatin analogs with Phe(3) residue modifications.

A FGLamide allatostatin neuropeptide mimic (H17) is a potential insect growth regulator which inhibits the production of juvenile hormone by the corpora allata. To find more evidence to reveal the structure-activity relationships of the Phe(3) residue in the C-terminal conserved pentapeptide and search for novel analogs with high activity, a series of Phe(3) residue-modified analogs were designed and synthesized using H17 as the lead compound. Bioassay using juvenile hormone (JH) production by corpora allata of the cockroach Diploptera punctata indicated that analogs 4, 11, and 13 showed strong ability to inhibit JH production in vitro, with IC50 of 38.5, 22.5, and 26 nM, respectively. As well, the activity of analog 2 (IC50 : 89.5 nM) proved roughly equivalent to that of H17. Based on the primary structure-activity relationships of Phe(3) residue, we suggest that for analogs containing six-membered aromatic rings, removing the methylene group of Phe(3) or an o-halogen or p-halogen-substituted benzene ring could increase the ability to inhibit biosynthesis of JH. This study will be useful for the design of new allatostatin analogs for insect management. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

In silico and bio assay of juvenile hormone analogs as an insect growth regulator against Galleria mellonella (wax moth) – Part I

Juvenile hormone (JH) analogs are nowadays in use to control harmful pests. In order to develop new bioactive molecules as potential pesticides, we have incorporated different active structural features like sulfonamide, aromatic rings, amide group, and amino acid moiety to the base structure. We have screened a series of designed novel JH analogs against JH receptor protein (jhbpGm-2RCK) of Galleria mellonella in comparison to commercial insect growth regulators (IGRs) – Pyriproxyfen (T1) and Fenoxycarb (T2). All analogs exhibit the binding energy profile comparable to commercial IGRs. Based upon these results, a series of sulfonamide-based JHAs (T3–T8) as IGRs have been synthesized and characterized. Further, the efficacy of synthesized analogs (T3–T8) and commercial IGRs (Pyriproxyfen and Fenoxycarb) has been assessed against fourth instars larvae of G. mellonella under the laboratory conditions. LC50 values of all the analogs (T1–T8) against the fourth instars larvae were 9.99, 10.12, 24.76, 30.73, 38.45, 34.15, 34.14, 19.48 ppm and the LC90 153.27, 131.69, 112.15, 191.46, 427.02, 167.13, 217.10, 172.00 ppm, respectively. Among these analogs, N-(1-isopropyl-2-oxo-3-aza-3-N-ethyl-pentanyl)-p-toluene sulfonamide (T8) and N-(1-isopropyl-2-oxo-3-aza-3-N-ethyl-pentanyl) benzene sulfonamide (T7) exhibited the good pest larval mortality at different exposure periods (in hours) and different concentrations (in ppm) in comparison to in use IGRs- T1 and T2. Bio assay results are supported by docking at higher concentration. The present investigation clearly exhibits that analog T8 could serve as a potential IGR in comparison to in use IGRs (T1 and T2). The results are promising and provide new array of synthetic chemicals that may be utilized as IGRs.

Synthesis, bioactivity and functional evaluation of linker-modified allatostatin analogs as potential insect growth regulators

Abstract Insect growth regulators play an important role in integrated pest management strategies. The FGLa–allatostatins (ASTs) are a family of neuropeptides that can inhibit juvenile hormone (JH) biosynthesis by the corpora allata (CA) of Diploptera punctata in vitro, are regarded as insect growth regulator candidates. In the search for new potential mimics and to explore the effect of linker length on inhibiting JH biosynthesis, a series of AST analogs were synthesized by modifying the linker of K24, which was found to have a significant effect on JH biosynthesis in vitro in our previous study. Functional evaluation demonstrated that all the target compounds can activate the Dippu-AstR, albeit with different potencies. Analog L6 with the longest linker (n = 5), exhibited not only a promising effect on inhibition of JH biosynthesis both in vitro and in vivo, but also good activity in inhibiting basal oocyte growth. Structure–activity relationships (SAR) studies showed that longer linkers provided greater contribution to activity.

Synthesis, biological activity, and conformational study of N-methylated allatostatin analogues inhibiting juvenile hormone biosynthesis.

An allatostatin (AST) neuropeptide mimic (H17) is a potential insect growth regulator, which inhibits the production of juvenile hormone (JH) by the corpora allata. To determine the effect of conformation of novel AST analogues and their ability to inhibit JH biosynthesis, eight insect AST analogues were synthesized using H17 as the lead compound by N-methylation scanning, which is a common strategy for improving the biological properties of peptides. A bioassay using JH production by corpora allata of the cockroach Diploptera punctata indicated that single N-methylation mimics (analogues 1-4) showed more activity than double N-methylation mimics (analogues 5-8). Especially, analogues 1 and 4 showed roughly equivalent activity to that of H17, with IC50 values of 5.17 × 10(-8) and 6.44 × 10(-8) M, respectively. Molecular modeling based on nuclear magnetic resonance data showed that the conformation of analogues 1 and 4 seems to be flexible, whereas analogues 2 and 3 showed a type IV β-turn. This flexible linear conformation was hypothesized to be a new important and indispensable structural element beneficial to the activity of AST mimics.

Peptidomimetics in the Discovery of New Insect Growth Regulators: Studies on the Structure−Activity Relationships of the Core Pentapeptide Region of Allatostatins

Cockroach-type allatostatins (ASTs) were discovered in cockroaches through their capacity to inhibit the production of juvenile hormone by the corpora allata (CA). ASTs were considered as potential insect growth regulator (IGR) candidates, but several disadvantages, including the absence of the effect in vivo and rapid degradation in vivo, precluded their application in pest management. The CA were selected as the target, and the core pentapeptide region (YDFGL) was chosen as the lead sequence in the search for new IGRs based on the allatostatins. We designed and synthesized 24 analogues, which mimicked each amino acid of the core region, to determine structure-activity relationships and the possibility of shortening the ASTs in the core region while retaining activity. The results suggest that the sequence FGLa is more important than Y/FX because Y/FX mimics show strong effects in vitro and in vivo. In particular, compound I3 was synthesized by substitution of Y/FX with 6-phenylhexnoic acid and exhibits higher activity in vitro than the complete core region. Furthermore, compound I3 has a clear effect in vivo on juvenile hormone (JH) biosynthesis of Diploptera punctata females, providing a possible application for cockroach management. On the basis of the structure-activity relationship of pentapeptide analogues, a general structure of potential potent AST analogues is proposed here. A new approach using peptidomimetics in the discovery of IGRs is demonstrated in our study.

ChemInform Abstract: Design and Synthesis of Novel N′‐tert‐Butyl‐N′‐substitutedbenzoyl‐N‐ [dihydrobenzofuran(chroman)]carbohydrazide Derivatives as Potential Insect Growth Regulators.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A potential insect growth regulator: Synthesis and bioactivity of an allatostatin mimic

Insect growth regulators play an important role in Integrated Pest Management systems. Cockroach-type allatostatins (FGLamides) (ASTs), which are a family of basic peptides first isolated from brains of Diploptera punctata were originally discovered on the basis of their ability to inhibit the production of juvenile hormone by the corpora allata. For this reason, the ASTs can be regarded as possible IGR candidates for pest control although the absence of effect in vivo, rapid degradation and high production costs of the natural peptides preclude their use in pest management. However, we have synthesized a new AST mimic, H17, from the pentapeptide C-terminal active core of the AST. This mimic is able to significantly inhibit the biosynthesis of JH by cockroach CA in vitro (IC 50 value: 12 nM) and in vivo following injection (IC 50 value: 33 nM). H17 also shows a highly significant inhibition of JH production in topical cuticular assays in vivo. Our results suggest that H17 has potential as an IGR for cockroach control.

Design and Synthesis of Novel N-tert-butyl-N-substitutedbenzoyl-N- [dihydrobenzofuran(chroman)]carbohydrazide Derivatives as Potential Insect Growth Regulators

Six of new N-tert-butyl-N-substitutedbenzoyl-N-(2,4-dimethyl-2,3-dihydrobenzofuran)-7-carbohydrazide derivatives and five of new N-tert-butyl-N-substitutedbenzoyl-N-(5-methylchroman)-8-carbohydrazide derivatives were designed and synthesized from m-cresol. The synthesis highlighted that some kinds of reactions were ameliorated in methodology. An important feature is that 1-(3-allyl-2-hydroxy-4-methylphenyl)ethanone can easily be transformed into 1-(2,3-dihydro-2,4-dimethylbenzofuran-7-yl)ethanone just with concentrated sulfuric acid as catalyst. In addition, we found that 1-(5-methyl-2H-chromen-8-yl)ethanone could not be reduced to 1-(5-methylchroman-8-yl)ethanone directly by hydrogen with Pd/C as catalyst. It is an effective method for protecting 1-(5-methyl-2H-chromen-8-yl)ethanone with ethylene glycol to obtain 5-methyl-8-(2-methyl-1,3-dioxolan-2-yl)-2H-chromene and then reducing by hydrogen with Pd/C as catalyst to produce 1-(5-methylchroman-8-yl)ethanone in one step. Furthermore, SOCl2 can convert 2,3-dihydro-2,4- dimethylbenzofuran-7-carboxylic acid to 2,3-dihydro-2,4-dimethylbenzofuran-7-carbonyl chloride, but it is inefficient for transforming 5-methylchroman-8-carboxylic acid to the corresponding acyl chloride. Hence, different heterocycles on the benzene ring of benzoheterocyle moiety have influence on the reaction property of the corresponding acid.

Screening of environmental contaminants for ecdysteroid agonist and antagonist activity using the Drosophila melanogaster BII cell in vitro assay

AbstractThe BII bioassay was developed as a rapid and reliable tool for detecting potential insect growth regulators acting as ecdysteroid receptor (ant)agonists. Based on an ecdysteroid‐responsive cell line from Drosophila melanogaster, this microplate assay is ideally suited to the evaluation of environmental contaminants as potential endocrine disrupters. Data are presented for about 80 potential environmental contaminants, including industrial chemicals, pesticides, Pharmaceuticals, phytoestrogens, and vertebrate steroids, and are compared with data for known (ant)agonists. Apart from androst‐4‐ene‐3,17‐dione (a weak antagonist), vertebrate steroids were inactive at concentrations up to 10−3 M. The vast majority of xenobiotics also showed no (ant)agonist activity. Among the industrial chemicals, antagonistic activity was observed for bisphenol A median effective concentration (EC50) of 1.0 × 10−4 M and diethylphthalate (EC50 of 2.0 × 10−3 M). Some organochlorine compounds also showed weak antagonistic activity, including o,p′‐dichlorodiphenyldichloroethylene (DDE), p,p′‐DDE, dieldrin, and lindane (EC50 of 3.0 × 10−5 M). For lindane, bisphenol A, and diethylphthalate, activity is not associated with impurities in the samples and, for lindane and bisphenol A at least, the compounds are able to compete with ecdysteroids for the ligand binding site on the receptor complex, albeit at concentrations very much higher than those found in the environment. The only pharmaceutical showing any detectable antagonist activity was 17α‐ethynylestradiol. In the context of recent publications on potential endocrine disruption in marine and freshwater arthropods, these findings suggest that, for some compounds (e.g., diethylstilbestrol), ecdysteroid receptor‐mediated responses are unlikely to be involved in producing chronic effects. The BII assay has a potentially valuable role to play in distinguishing between endocrine‐mediated, which normally occur at submicromolar concentrations, and pharmacological effects in insects and crustaceans.

Screening of environmental contaminants for ecdysteroid agonist and antagonist activity using the Drosophila melanogaster B(II) cell in vitro assay.

The B(II) bioassay was developed as a rapid and reliable tool for detecting potential insect growth regulators acting as ecdysteroid receptor (ant)agonists. Based on an ecdysteroid-responsive cell line from Drosophila melanogaster, this microplate assay is ideally suited to the evaluation of environmental contaminants as potential endocrine disrupters. Data are presented for about 80 potential environmental contaminants, including industrial chemicals, pesticides, pharmaceuticals, phytoestrogens, and vertebrate steroids, and are compared with data for known (ant)agonists. Apart from androst-4-ene-3,17-dione (a weak antagonist), vertebrate steroids were inactive at concentrations up to 10(-3) M. The vast majority of xenobiotics also showed no (ant)agonist activity. Among the industrial chemicals, antagonistic activity was observed for bisphenol A median effective concentration (EC50) of 1.0 x 10(-4) M and diethylphthalate (EC50 of 2.0 x 10(-3) M). Some organochlorine compounds also showed weak antagonistic activity, including o,p'-dichlorodiphenyldichloroethylene (DDE), p,p'-DDE, dieldrin, and lindane (EC50 of 3.0 x 10(-5) M). For lindane, bisphenol A, and diethylphthalate, activity is not associated with impurities in the samples and, for lindane and bisphenol A at least, the compounds are able to compete with ecdysteroids for the ligand binding site on the receptor complex, albeit at concentrations very much higher than those found in the environment. The only pharmaceutical showing any detectable antagonist activity was 17alpha-ethynylestradiol. In the context of recent publications on potential endocrine disruption in marine and freshwater arthropods, these findings suggest that, for some compounds (e.g., diethylstilbestrol), ecdysteroid receptor-mediated responses are unlikely to be involved in producing chronic effects. The B(II) assay has a potentially valuable role to play in distinguishing between endocrine-mediated, which normally occur at submicromolar concentrations, and pharmacological effects in insects and crustaceans.

Toxicity of Neem Applied Alone and in Combinations with Bacillus thuringiensis to Colorado Potato Beetle (Coleoptera: Chrysomelidae)

The toxicity of neem (Neemix, 0.25% azadirachtin [AI]) and combinations of neem and Bacillus thuringiensis was examined on 2nd instar of the B. thuringiensis susceptible (Bt-S) and resistant (Bt-R) strains of Colorado potato beetle, Leptinotarsa decemlineata (Say). Using a potato leaf-dipping method, the LC50 values of neem determined 2 d posttreatment to larvae of the Bt-S and Bt-R were 2.07 and 6.56 mg (AI)/liter, respectively. The LC50 values in both strains decreased significantly with increased exposure time. Cross-resistance between these toxins was not evident with a resistance ratio ranging from 1.3–3.2. Combinations of sublethal concentrations of neem (0.45 or 0.25 mg [AI]/liter) with a sublethal concentration of B. thuringiensis (0.74 mg [AI]/liter) to larvae of the Bt-S yielded an additive effect in larval mortality. In contrast, combinations of neem (0.78 or 0.43 mg [AI]/liter) and B. thuringiensis (319.8 mg [AI]/liter) resulted in a synergistic effect to larvae of the Bt-R strain. Sublethal concentrations of neem or B. thuringiensis applied separately or in combinations decreased the mean larval weight and retarded the larval growth of both strains. Our results suggest that neem is a potential insect growth regulator on larvae of the Bt-S and Bt-R and a possible B. thuringiensis resistance breaking compound. Field trials to determine the performance of neem in combination with B. thuringiensis on field populations of Colorado potato beetle are warranted.

Effect of the Nonsteroidal Ecdysone Agonists, Methoxyfenozide and Tebufenozide, on the European Corn Borer (Lepidoptera: Pyralidae)

The effect of 2 nonsteroidal ecdysone agonists, methoxyfenozide (proposed name for RH-2485) and tebufenozide (RH-5992), was examined on eggs and larvae of the European corn borer, Ostrinia nubilalis (Hubner). Both compounds were ovicides. More than 90% of eggs died when egg masses were dipped in a solution of 100 ppm methoxyfenozide or tebufenozide in acetone:distilled water (1:1). Although some eggs that were treated with 1 or 10 ppm methoxyfenozide or tebufenozide hatched, the survival rate was low. Test compounds were incorporated into an artificial diet to examine larvicidal effects. Using this technique, methoxyfenozide was 3-7 times more toxic to newly hatched larvae than was tebufenozide. Methoxyfenozide was 184-270 and 147-469 times more toxic to newly hatched larvae than were diflubenzuron and carbaryl, respectively, whereas tebufenozide was 41-68 and 22-75 times more toxic than were diflubenzuron and carbaryl, respectively. Methoxyfenozide was toxic to 3rd instars with the LC50 value being ≈2 times higher than it was for newly hatched larvae. Methoxyfenozide (0.125 and 0.25 ppm) and tebufenozide (0.25 and 0.5 ppm) were lethal to newly hatched larvae, even after diets containing these compounds were held for 20 d under long days (16:8 [L:D] h) at 30°C. Tebufenozide applied at 0.016 and 0.031 ppm to larvae inhibited larval growth, delayed pupation, and decreased adult emergence. Methoxyfenozide applied at 0.063, 0.125, 0.25, and 0.5 ppm to newly ecdysed 4th instars caused them to stop feeding ≈8 h after exposure and induced a premature and lethal molting cycle. Methoxyfenozide and tebufenozide are potential insect growth regulators for controlling O. nubilalis .