Juvenile hormone esterase inhibition

Herbert Oberlander coordinated the section that features chapters on sac-specific selection using chimeric genes potential applications of neuroendocrine research to insect control insect cuticle structure and metabolism molecular aspects of immune mechanisms in insects molecular genetics of nerve insensitivity resistance to insecticides and inhibition of juvenile hormone esterase by transition-state analogs. 

Inhibition of Juvenile Hormone Esterase by Transition-State Analogs... 

A new series of compounds, a,a -alkanebis-thiotrifluoro-propanones was synthesized and showed excellent in vitro and moderate in vivo inhibition of the insect juvenile hormone esterase from the fifth instar larvae of Trichoplusia ni (cabbage looper). The potency of the above series was also screened for its ability to inhibit other esterases of toxicological and pharmacological significance. Trifluoroketones are discussed as an example of the importance of chemistry in biotechnology approaches. 

Methods have been published that allow the classification of two types of esterases, the carboxylic ester hydrolases (CEHs) and the phosphoric triester hydrolases (PTEHs) (Anspaugh and Roe, 2004). The CEHs contain the B-esterases, which are inhibited by organophosphates. B-esierases include many other esterases, such as CarbE, acetylcholinesterase (AChE), cholinesterases (ChE), aryleslerases, sterol esterases, insect juvenile hormone esterases, aixl others. The determination of A-esterases uses a protocol for the detection of PTEHs. The PTEH assay allows for the identification of two subclasses of esterases, the A-esterase (known as aiyldialkylphos-phatase) and ditsopropyl fluorophosphatase. Both these enzymes metabolize OP compounds. 

Trifluoromethyl ketones (TFKs) have been found to inhibit various hydrolytic enzymes (1-6 ). Series of aliphatic and aromatic trifluoromethyl ketone sulfides (7-10 ) proved to be exceptionally powerful inhibitors of insect juvenile hormone esterase (JHE), an enzyme of key importance in insect metamorphosis. The trifluoroketone moiety is believed to behave as a transition state mimic (11,12) of juvenile hormones (JHs), substrates of the enzyme. The /3 sulfur atom is anticipated to mimic the a-/3 double bond present in all natural JH substrates. In earlier structure-activity relationship (SAR) studies (7,11) clear correlation was found among the molar I50 values of these compounds against JHE and the calculated molar refractivlty of the inhibitors. 

Table I. Inhibition of Insect juvenile hormone esterase by arylthio-trlfluoropropanones of structure A...

Esterases of the Juvenile Hormone of Insects Many works have been dedicated to the inhibition of esterases of the juvenile hormone of insects. The purpose of these works is to control insect populations by ehminating their metamorphosis. Among the numerous trifluoromethyl ketones that have been synthesized, thioalkyl derivatives of trifluoroacetone have been shown to be the most active ones. Curiously, the corresponding alcohols are also excellent inhibitors. Trifluoromethyl ketones can also inhibit other insect esterases antenna esterases and esterases that are involved in the release of pheromones (Figure 7.33). The inhibition of these latter ones can also be interesting for insect control purposes. 

Hammock and co-workers (Hammock et ai, 1982 Abdel-Aal, 1984 Prestwich et ai, 1984) prepared several 3-alkylthio-l,l,l-trifluoro-2-propanones with juvenile hormone-like side chains. These compounds were designed as possible transition-state analogue inhibitors of JH esterases. The most active analogue (78) showed a dose-dependent delay in pupation and a selective inhibition of JH esterase of the cabbage looper, Trichopltisia ni. 

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