Accession Number:

ADA202378

Title:

Inhibition of Xenobiotic-Degrading Hydrolases by Organophosphinates

Descriptive Note:

Final rept. 1 Jul 1982-30 Jun 1986, annual rept. Jul 1985-Jun 1986

Corporate Author:

CLEMSON UNIV SC DEPT OF ENTOMOLOGY FISHERIES AND WILDLIFE

Report Date:

1986-07-01

Pagination or Media Count:

118.0

Abstract:

An abridged synthesis of 4-nitrophenyl diphenylphosphinate is described in which this compound was prepared in two steps. Chromatographic characteristics of four series of 4-nitrophenyl organophosphinates are described including results on normal-phase, reversed-phase and chiral-phase columns. Enantiomers of four organophosphinates were separated on a commercial R-N-3, 5-dinitrobenzoylphenylglycine chiral-phase column. Analysis of 4-nitrophenyl diphenylphosphinate was performed after administration to mice and after incubation with rabbit serum. Porcine liver carboxylester hydrolase carboxylesterase was rapidly inhibited by 4-nitrophenyl organophosphinates containing aryl or heteroaryl groups directly bound to phosphorus. The most potent inhibitor was 4-nitrophenyl di-2-thienylphosphinate. Concentration of CARBOXYL- CARBON 14 procaine in blood on mice were increased three-fold for 27 min by exposure to 0-4-nitrophenyl diphenylphosphinate 2 h prior to CARBOXYL- CARBON 14 procaine injection ip. The substrate specificity of arylester hydrolase partially purified from rabbit serum was studied. Acetylcholinesterases from electric eel and from bovine erythrocytes were inhibited stereoselectively by P4-nitrophenyl ethyl phenyl EPP and P 4-nitrophenyl isopropyl phenylphosphinate IPP. Phosphorylase kinase from rabbit muscle appeared to have catalytic activity toward EPP. Keywords Enzyme inhibitors, Organophosphinate pretreatment agents, Enzyme reactivation, Drug interaction, Stereoselectivity.

Subject Categories:

  • Biochemistry
  • Pharmacology
  • Organic Chemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE