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- Title
THREE-DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP AND COMPARATIVE MOLECULAR FIELD ANALYSIS OF CYP450 ENZYME SYSTEM INHIBITORS.
- Authors
Ananthula, Ravi Shekar; Gade, Swetha; Mahmood, S. K.
- Abstract
"cytochrome P450" family of enzymes are present in every cell and are responsible for biotransformation of drugs from active to inactive metabolites that are readily excreted by the body., the rapid metabolism of certain drugs by the CYP450 enzyme system can markedly alter their pharmacokinetic (PK) profile and can result in sub-therapeutic plasma levels of those drugs over time. To understand the ligand structural requirements and to enhance inhibitory potency for new ligands against CYP-450 enzyme system, 3D- QSAR comparative molecular field analysis (CoMFA) study was carried out on a series of 2-[3-(4-fluorobenzyl)-5-pyridin-4-yl-1H-pyrazol-1-yl] derivatives, as selective CYP- 450 enzyme system inhibitors. Comparative molecular field analysis (CoMFA) QSAR models were computed with Sybyl 6.7v. The developed model gave leave-one-out (LOO) cross-validated correlation coefficient q2 value of 0.844, non-cross-validated correlation coefficient r2 value of 0.992, and the predicted correlation coefficient r2pred was found to be 0.781. The QSAR model gave satisfactory statistical results in terms of q2 and r2 values. The CoMFA model provided the most significant correlation of steric and electrostatic fields with biological activities. The information derived from this study provides a tool for guiding further structural modification to obtain selective inhibitors of CYP450.
- Publication
Pharma Science Monitor, 2013, Vol 4, Issue 2, p3890
- ISSN
0976-9242
- Publication type
Academic Journal