QSAR studies on peptide α-ketoamides and α-ketohydroxamate derivatives as calpain I inhibitors

Abstract

Quantitative Structure Activity Relationship (QSAR) studies were conducted on 34 peptide α-ketoamide and α-ketohydroxamate derivatives of Calpain I using multiple linear regression (MLR) procedure. The activity contributions of these compounds were determined from regression equation and the validation procedures that analyze the predictive ability of QSAR models were described. Among forty six descriptors that were considered in generating the QSAR model, three descriptors such as LogP, Heat of formation and HOMO resulted in a statistically significant model with 0.877 r2 and 0.937 q2 respectively. The inter-correlation between descriptors was 0.42. The proposed QSAR model indicates an increase in logP value increases hydrophobicity in order to achieve cellular permeability and an increase in heat of formation as well as decrease in HOMO energy favors better binding and activity towards development of potent calpain I inhibitors.