Interaction of a series of nitriles with the alcohol-inducible isoform of P450: computer analysis of structure-activity relationships.
1. Structural studies are reported on a series of 20 nitriles of varying rates of P4502E-mediated oxidative metabolism. 2. Parameters of molecular and electronic structure have been calculated for the generation of quantitative structure-activity relationships (QSARs) with the rates of oxidative metabolism of the nitriles, and with their acute toxicity. 3. Correlations between molecular polarizability, excitation energy and biological activity are presented as a result of QSAR analysis.
Lewis
D F
DF
School of Biological Sciences, University of Surrey, Guildford, UK.
Ioannides
C
C
Parke
D V
DV
D001711:Biotransformation; D003198:Computer Simulation; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000378:metabolism*; D008954:Models, Biological; D009570:Nitriles / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D010084:Oxidation-Reduction; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis* / Q000378:metabolism*; D011237:Predictive Value of Tests; D013329:Structure-Activity Relationship
D007527:Isoenzymes; D009570:Nitriles; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; C071207:1,2-dimethylhydrazine demethylase; D010089:Oxidoreductases, N-Demethylating