Synthesis and bioassay of isoprenoid 3-alkylthio-1,1,1-trifluoro-2-propanones: Potent, selective inhibitors of juvenile hormone esterase

Glenn D. Prestwich, Wai Si Eng, R. Michael Roe, Bruce D. Hammock

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Abstract

Four 3-alkylthio-1,1,1-trifluoro-2-propanones with juvenile hormone-like side chains were prepared from citronellol and homogeraniol. These substrates were designed as possible transition-state analogs for the juvenile hormone (JH)-specific esterases present in insects. These four isoprenoid trifluoromethyl ketones were assayed in vitro with JH esterase and general esterases from larvae of the cabbage looper, Trichoplusia ni (Lepidoptera, Noctuidae), and with eel acetylcholinesterase and bovine chymotrypsin. JH esterase inhibition I50 values were in the nanomolar range for all four compounds, while the other esterases had I50'S which were 103 to 105 higher. The high selectivity of these inhibitors is believed to be due to their similarity in size and functionality to natural JH III. Treatment of T. ni larvae in vivo with solutions of the most active analog, 3-[(E)-4,8-dimethyl-3,7-nonadienylthio]-1,1,1-trifluoro-2-propanone (DNTFP) causes a dose-dependent delay in pupation and a concurrent selective inhibition of JH esterase. These data support the hypothesis that the reduction in in vivo JH titer in larval T. ni is due, in part, to hydrolysis of the hormone by selective esterases. DNTFP appears to be competing with JH for the active site of JH esterase.

Original languageEnglish (US)
Pages (from-to)639-645
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume228
Issue number2
DOIs
StatePublished - Feb 1 1984

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Juvenile Hormones
Bioassay
Terpenes
Esterases
Acetone
Biological Assay
Lepidoptera
Larva
Chymotrypsin
Acetylcholinesterase
Eels
Ketones
Brassica
Hydrolysis
Hormones
Insects
Catalytic Domain
juvenile hormone esterase
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Synthesis and bioassay of isoprenoid 3-alkylthio-1,1,1-trifluoro-2-propanones : Potent, selective inhibitors of juvenile hormone esterase. / Prestwich, Glenn D.; Eng, Wai Si; Roe, R. Michael; Hammock, Bruce D.

In: Archives of Biochemistry and Biophysics, Vol. 228, No. 2, 01.02.1984, p. 639-645.

Research output: Contribution to journalArticle

Prestwich, Glenn D. ; Eng, Wai Si ; Roe, R. Michael ; Hammock, Bruce D. / Synthesis and bioassay of isoprenoid 3-alkylthio-1,1,1-trifluoro-2-propanones : Potent, selective inhibitors of juvenile hormone esterase. In: Archives of Biochemistry and Biophysics. 1984 ; Vol. 228, No. 2. pp. 639-645.
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