Insights into the structure of urea-like compounds as inhibitors of the juvenile hormone epoxide hydrolase (JHEH) of the tobacco hornworm Manduca sexta: Analysis of the binding modes and structure–activity relationships of the inhibitors by docking and CoMFA calculations

Garriga, Miguel; Caballero, Julio

doi:10.1016/j.chemosphere.2010.11.048

Cited by 28 publications

(21 citation statements)

References 39 publications

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“…In independent research, closely related synthetic compounds have been previously described as inhibitors of insect juvenile hormone epoxide hydrolase (JHEH). [12][13][14] In conjunction with juvenile hormonee sterase (JHE), JHEH is ak ey player in the degradation of juvenile hormone (JH), which regulates both growth andd evelopment of insect larvae and reproductive functions of adults, [15] and is also produced by the plant Cyperiusi ria as ad efence mechanism against insects. [16] Importantly, P. luminescens phurealipids and the related synthetic insecticides are structurally similar to JH (Scheme 2), thus suggesting ap ossible mode of action.…”

Section: Resultsmentioning

confidence: 99%

A Photorhabdus Natural Product Inhibits Insect Juvenile Hormone Epoxide Hydrolase

et al. 2015

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Simple urea compounds (“phurealipids”) have been identified from the entomopathogenic bacterium Photorhabdus luminescens, and their biosynthesis was elucidated. Very similar analogues of these compounds have been previously developed as inhibitors of juvenile hormone epoxide hydrolase (JHEH), a key enzyme in insect development and growth. Phurealipids also inhibit JHEH, and therefore phurealipids might contribute to bacterial virulence.

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Section: Resultsmentioning

confidence: 99%

A Photorhabdus Natural Product Inhibits Insect Juvenile Hormone Epoxide Hydrolase

et al. 2015

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“…Models that are capable to explain the interactions and predict the biological activity of compounds by their structural properties have been considered as powerful tools to design highly active molecules. In molecular docking, we attempt to predict the structure (or structures) of the intermolecular complex formed between two or more molecules [11,12]. Phenoxy derivative of JHAs found to be more bio effective, in comparison to the terpenoid JHAs [13].…”

Section: Resultsmentioning

confidence: 99%

Designing and Binding Mode Prediction of Juvenile Hormone Analogues as Potential Inhibitor for Galleria mellonella

Awasthi¹,

Sharma²

2013

J Comput Sci Syst Biol

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Virtual screening of chemical databases has become an integral part of ligand design. Docking is one of the most important methods in computer assisted screening. If a three dimensional structure of target receptor is available, along with information regarding nature of the ligand-binding site, ligand-binding mode; the interactions between the ligand and receptor can be studied extensively, in order to design and develop target specific new compounds in a short time period. Juvenile Hormone Analogues, sesqui-terpenoid series of compound act as an insect growth regulator, and presently in use as a potential environment friendly pesticide. Juvenile hormone is the molting hormone responsible for each molt, and involved in a wide range of physiological processes in both developing and mature insect. Designing of various juvenile hormone analogues are new and emerging area to counter the insect problem.In this paper, we report protein-ligand interactions using a standard protocol of docking. We perform screening of synthesized (A-B) and proposed (C-D) series of Juvenile Hormone Analogues with hemolymph binding proteins of Galleria mellonella. Further binding energy profile of all the series have been compared with the phenoxy derivatives of juvenile hormone mimics, as well as natural JH III, in order to design targeted JHAs with improved biological activities. Our proposed series of juvenile hormone analogues exhibit better energy profile over in use phenoxy derivatives.

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“…3). In addition, JH-like urea compounds which are generally good inhibitors of MsJHEH (Severson et al, 2002; Garriga and Caballero, 2011) were poor inhibitors of Hv-mEH1 (Table 3). The JH-like secondary amide compounds also followed this trend with the highly potent MsJHEH inhibitors showing significantly lower potency against Hv-mEH1 (Table 3).…”

Section: Resultsmentioning

confidence: 99%

Cloning and characterization of a microsomal epoxide hydrolase from Heliothis virescens

Kamita

Yamamoto

Dadala

et al. 2013

Insect Biochemistry and Molecular Biology

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Epoxide hydrolases (EHs) are α/β-hydrolase fold superfamily enzymes that convert epoxides to 1,2-trans diols. In insects EHs play critical roles in the metabolism of toxic compounds and allelochemicals found in the diet and for the regulation of endogenous juvenile hormones (JHs). In this study we obtained a full-length cDNA, hvmeh1, from the generalist feeder Heliothis virescens that encoded a highly active EH, Hv-mEH1. Of the 10 different EH substrates that were tested, Hv-mEH1 showed the highest specific activity (1,180 nmol min−1 mg−1) for a 1,2-disubstituted epoxide-containing fluorescent substrate. This specific activity was more than 25- and 3,900-fold higher than that for the general EH substrates cis-stilbene oxide and trans-stilbene oxide, respectively. Although phylogenetic analysis placed Hv-mEH1 in a clade with some lepidopteran JH metabolizing EHs (JHEHs), JH III was a relatively poor substrate for Hv-mEH1. Hv-mEH1 showed a unique substrate selectivity profile for the substrates tested in comparison to those of MsJHEH, a well-characterized JHEH from M. sexta, and hmEH, a human microsomal EH. Hv-mEH1 also showed unique enzyme inhibition profiles to JH-like urea, JH-like secondary amide, JH-like primary amide, and non-JH-like primary amide compounds in comparison to MsJHEH and hmEH. Although Hv-mEH1 is capable of metabolizing JH III, our findings suggest that this enzymatic activity does not play a significant role in the metabolism of JH in the caterpillar. The ability of Hv-mEH1 to rapidly hydrolyze 1,2-disubstituted epoxides suggests that it may play roles in the metabolism of fatty acid epoxides such as those that are commonly found in the diet of Heliothis.

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Insights into the structure of urea-like compounds as inhibitors of the juvenile hormone epoxide hydrolase (JHEH) of the tobacco hornworm Manduca sexta: Analysis of the binding modes and structure–activity relationships of the inhibitors by docking and CoMFA calculations

Cited by 28 publications

References 39 publications

A Photorhabdus Natural Product Inhibits Insect Juvenile Hormone Epoxide Hydrolase

A Photorhabdus Natural Product Inhibits Insect Juvenile Hormone Epoxide Hydrolase

Designing and Binding Mode Prediction of Juvenile Hormone Analogues as Potential Inhibitor for Galleria mellonella

Cloning and characterization of a microsomal epoxide hydrolase from Heliothis virescens

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