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


Personal Author(s) : Brown, Thomas M ; Bryson, P K ; Grothusen, John R ; Joly, James M ; Payne, Gregory T


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a202378.pdf


Report Date : Jul 1986


Pagination or Media Count : 118


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-dinitrobenzoyl)phenylglycine 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 P(=)4-nitrophenyl ethyl (phenyl) (EPP) and P(=) 4-nitrophenyl isopropyl (phenyl)phosphinate (IPP). Phosphorylase kinase from rabbit muscle appeared to have catalytic activity toward EPP. Keywords: Enzyme inhibitors, Organophosphinate pretreatment agents, Enzyme reactivation, Drug interaction, Stereoselectivity.


Descriptors :   *PHOSPHINATES , *ENZYME INHIBITORS , *ORGANIC PHOSPHORUS COMPOUNDS , CATALYSTS , MUSCLES , MICE , LIVER , DRUGS , BLOOD SERUM , INHIBITION , ERYTHROCYTES , BOVINES , PHOSPHORUS , ACETYLCHOLINESTERASE , CHOLINESTERASE INHIBITORS , POTENCY , BLOOD , RABBITS , SWINE , PEPTIDE HYDROLASES , ELECTRIC CHARGE , HYDROLASES , BIOCHEMICAL REACTIVATION , CARBOXYLIC ESTER HYDROLASES , CHROMATOGRAPHS , EELS , INCUBATION , PHOSPHORYLASES , INTERACTIONS , ENZYMES


Subject Categories : Biochemistry
      Pharmacology
      Organic Chemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE