A novel geminal diol as a highly specific and stable in vivo inhibitor of insect juvenile hormone esterase

Roe, R. Michael; Anspaugh, Douglas D.; Venkatesh, Krishnappa; Linderman, Russell J.; Graves, David M.

doi:10.1002/(sici)1520-6327(1997)36:3<165::aid-arch2>3.0.co;2-t

Cited by 23 publications

(29 citation statements)

References 40 publications

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“…[87][88][89][90][91][92][93] Several of these inhibitors including O-ethyl-Sphenyl phosphoramidothiolate (EPPAT) and 1-octyl[1-(3,3,3trifluoropropan-2,2-dihydroxy)]sulfone (OTFPdOH-sulfone, Fig. 3) proved to delay the metamorphosis of lepidopteran larvae, resulting in giant larvae.…”

Section: Inhibitors Of Metabolic Enzymesmentioning

confidence: 99%

“…3) proved to delay the metamorphosis of lepidopteran larvae, resulting in giant larvae. 91,94) The geometry of the active form of the TFK analogs required for esterase inhibition was unclear, but recent structure-activity relationship (SAR) studies indicated that these inhibitors work through the ketone as the active form rather than through the hydrated gem-diol. 95) The recent elucidation of the crystal structure of M. sexta JHE bound to 3-octylthio-1,1,1-trifluoropropan-2-one (OTFP) indicates that JHE has a long hydrophobic binding pocket with the three amino acids essential for enzymatic activity at the blind end which allows accessibility to the lipophilic JH molecule but not to the solvent.…”

Section: Inhibitors Of Metabolic Enzymesmentioning

confidence: 99%

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Insect juvenile hormone action as a potential target of pest management

Minakuchi

Riddiford

2006

J. Pestic. Sci.

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Juvenile hormone (JH) is a sesquiterpenoid hormone that regulates growth and development in insects. Since JH is a hormone specific to insects and other arthropods, compounds disrupting JH action in insects are expected to be ideal insecticides with low toxicity to non-target organisms. Many natural or synthetic analogs with JH-like or anti-JH activity have been identified, and some potent JH mimics have been used as insecticides. Recent studies on the enzymes in JH biosynthetic and metabolic pathways should be helpful for the discovery of more potent analogs and for the establishment of new means of pest management using recombinant DNA technology. © Pesticide Science Society of Japan Keywords: juvenile hormone (JH), insect metamorphosis, insect growth regulators, biosynthesis and metabolism of JH. Review* To whom correspondence should be addressed. E-mail: chieka_minakuchi@yahoo.com © Pesticide Science Society of Japan doptera. 17,18) Higher Diptera such as D. melanogaster and the blowfly Calliphora vomitoria produce JH III bisepoxide. 19,20) A small amount of methyl farnesoate, a precursor of JH III, was found in cockroach embryos and larvae. [20][21][22] Methyl farnesoate has also been identified in crustaceans 23) and is thought to have a JH-like action in female reproduction. 24)12Ј-OH JH III identified from the corpora allata of the African locust Locusta migratoria migratorioides was reported to exhibit JH activity when a high dose of this compound was topically applied to Tenebrio pupae. 25,26) Biosynthesis, Transport and Metabolism of Juvenile HormoneIn insects, JH is synthesized in the corpora allata via the mevalonate pathway (Fig. 2).27) The mevalonate pathway also exists in mammals and plants, and the early steps from acetylCoA to farnesyl diphosphate are conserved among these organisms. Importantly, insects and other arthropods do not synthesize cholesterol de novo but have to acquire it from dietary sources because they lack the genes encoding squalene synthase and other subsequent enzymes of the sterol branch. 28,29) Another peculiarity of the mevalonate pathway in insects is the capacity to synthesize JH via the isoprenoid branch.The genes encoding the enzymes in the mevalonate pathway from acetyl-CoA to farnesyl diphosphate have been identified in the genome of D. melanogaster and the malaria mosquito Anopheles gambiae, and in an EST library of the pine engraver Ips pini.27) However, it has been difficult to identify the genes encoding enzymes from farnesyl diphosphate to JH

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Section: Inhibitors Of Metabolic Enzymesmentioning

confidence: 99%

Section: Inhibitors Of Metabolic Enzymesmentioning

confidence: 99%

Insect juvenile hormone action as a potential target of pest management

Minakuchi

Riddiford

2006

J. Pestic. Sci.

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“…One possibility is that the sulfoxide-containing compounds are highly hydrated. It has been hypothesized that the ketone is the active form of the inhibitor (Wheelock et al, 2003); however, it has also been reported that potent inhibitors exist as their hydrated forms in aqueous solution (Roe et al, 1997). If both of these reports are accurate, then the equilibrium between the ketone and gem-diol forms of the inhibitor must be sufficiently dynamic such that adequate concentrations of the ketone are available for enzyme inhibition.…”

Section: Inhibition Of Carboxylesterases By Trifluoromethylketones 721mentioning

confidence: 99%

“…Of particular interest is the observation that in TFK-containing inhibitors or in more broadly polarized ketones, the polarization of the carbonyl group shifts the equilibrium toward the gem-diol form ( Fig. 1) (Roe et al, 1997).…”

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confidence: 99%

Analysis of Mammalian Carboxylesterase Inhibition by Trifluoromethylketone-Containing Compounds

Wadkins¹,

Hyatt²,

Edwards³

et al. 2006

Mol Pharmacol

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Carboxylesterases (CE) are ubiquitous enzymes that hydrolyze numerous ester-containing xenobiotics, including complex molecules, such as the anticancer drugs irinotecan (CPT-11) and capecitabine and the pyrethroid insecticides. Because of the role of CEs in the metabolism of many exogenous and endogenous ester-containing compounds, a number of studies have examined the inhibition of this class of enzymes. Trifluoromethylketone-containing (TFK) compounds have been identified as potent CE inhibitors. In this article, we present inhibition constants for 21 compounds, including a series of sulfanyl, sulfinyl, and sulfonyl TFKs with three mammalian CEs, as well as human acetyl-and butyrylcholinesterase. To examine the nature of the slow tight-binding inhibitor/enzyme interaction, assays were performed using either a 5-min or a 24-h preincubation period. Results showed that the length of the preincubation interval significantly affects the inhibition constants on a structurally dependent basis. The TFK-containing compounds were generally potent inhibitors of mammalian CEs, with K i values as low as 0.3 nM observed. In most cases, thioethercontaining compounds were more potent inhibitors then their sulfinyl or sulfonyl analogs. QSAR analyses demonstrated excellent observed versus predicted values correlations (r 2 ranging from 0.908 -0.948), with cross-correlation coefficients (q 2 ) of ϳ0.9. In addition, pseudoreceptor models for the TKF analogs were very similar to structures and models previously obtained using benzil-or sulfonamide-based CE inhibitors. These studies indicate that more potent, selective CE inhibitors, containing long alkyl or aromatic groups attached to the thioether chemotype in TFKs, can be developed for use in in vivo enzyme inhibition.

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“…Chemical synthesis has been the simplest and direct approach toward the development of new class of juvenile hormone analogs with juvenile hormone activity. Large number of juvenile hormone analogs (JHAs) have been synthesized in the literature and found to have potent JH activity against lepidopteran insects [5][6][7][8][9][10][11][12]. JH, hydrophobic hormone, is released from corpora allata and after passing through the plasma membrane binds to the receptor protein present in the cytoplasm or nucleus.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, Biological Evaluation and Docking Study of Heterocyclic-Based Synthetic Sulfonamides as Potential Pesticide Against G. mellonella

Sharma

Thakur

Awasthi

2015

Appl Biochem Biotechnol

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Juvenile hormone is an important hormone which controls the developmental process in the lepidopteran insects, hence, referred as insect growth regulator. Juvenile hormone binding proteins are the carrier of juvenile hormone from the site of secretion to the site of action and play vital role in juvenile hormone action. We have designed four different juvenile hormone analogs incorporating sulfonamide and heterocyclic moieties using computer-aided tools. All analogs (T3-T6) gave comparative energy profile in comparison to in use insect growth regulators like fenoxycarb (T2) and pyriproxyfen (T1). Further, theses analogs have been screened on biological model Galleria mellonella (wax moth) for their mortality rate. All analogs were evaluated using three different concentrations (1000, 1500, and 2000 ppm) and five different exposure periods (2, 4, 6, 8, and 10 h). In vivo study showed that analog N-(1-isopropyl-2-oxo-2-morpholino-ethyl) toluene sulfonamide (T6) and N-(1-isopropyl-2-oxo-2-piperidino-ethyl) toluene sulfonamide (T4) exhibit the good larval mortality at lower concentration (1000 ppm) after 8 h exposure in comparison to pyriproxyfen (T1) and fenoxycarb (T2). The findings demonstrate the effectiveness and validity of the virtual screening approach (docking) and provide a starting point for the development of novel juvenile hormone analogs to counter G. mellonella.

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A novel geminal diol as a highly specific and stable in vivo inhibitor of insect juvenile hormone esterase

Cited by 23 publications

References 40 publications

Insect juvenile hormone action as a potential target of pest management

Insect juvenile hormone action as a potential target of pest management

Analysis of Mammalian Carboxylesterase Inhibition by Trifluoromethylketone-Containing Compounds

Synthesis, Characterization, Biological Evaluation and Docking Study of Heterocyclic-Based Synthetic Sulfonamides as Potential Pesticide Against G. mellonella

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