Substituted thiotrifluoropropanones as potent selective inhibitors of juvenile hormone esterase

Bruce D. Hammock, Yehia A I Abdel-Aal, Christopher A. Mullin, Terry N. Hanzlik, Richard M. Roe

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

A series of 27 substituted thio-1,1,1-trifluoropropanones was synthesized by reacting the corresponding thiol with 1,1,1-trifluoro-3-bromopropanone. The resulting sulfides were screened as inhibitors of hemolymph juvenile hormone esterase and α-naphthyl acetate esterase activity of the cabbage looper, Trichoplusia ni, electric eel acetylcholinesterase, bovine trypsin, and bovine α-chymotrypsin. The presence of the sulfide bond increased the inhibitory potency on all of the enzymes tested when compared with compounds lacking the sulfide. In general, the compounds proved to be poor inhibitors of chymotrypsin and moderate inhibitors of trypsin. By varying the substituent on the sulfide, good inhibitory activity was obtained on α-naphthyl acetate esterase, acetylcholinesterase, while some of the compounds proved to be extremely powerful inhibitors of juvenile hormone esterase. The most powerful inhibitor tested was 3-octylthio-1,1,1-trifluoro-2-propanone, with an I50 of 2.3 × 10-9M on JH esterase. This compound showed a molar refractivity similar to that of the JH II backbone, was not toxic to T. ni, and was moderately toxic to mice, with a 48-hr LD50 of >750 mg/kg. It effectively delayed pupation when applied to prewandering larvae of T. ni, as expected for a JH esterase inhibitor. Thus, some members of this series are promising for evaluating the role of JH esterase in insect development. The series also indicates that, by varying the substituent on the sulfide moiety, potent "transition-state" inhibitors can be developed for a wide variety of esterases and proteases.

Original languageEnglish (US)
Pages (from-to)209-223
Number of pages15
JournalPesticide Biochemistry and Physiology
Volume22
Issue number2
DOIs
StatePublished - 1984

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Biochemistry
  • Physiology

Fingerprint Dive into the research topics of 'Substituted thiotrifluoropropanones as potent selective inhibitors of juvenile hormone esterase'. Together they form a unique fingerprint.

  • Cite this