QSAR Analysis for Some 1, 2-Benzisothiazol-3-one Derivatives as Caspase-3 Inhibitors by Stepwise MLR Method

Abstract

Caspase-3, one of the dominant effectors caspases, is activated in almost every model of apoptosis with various signaling pathways. Hence, inhibition of caspase-3 has become an attractive target in the treatment of neurodegenerative diseases. Caspase-3 inhibitory activities of some 1,2-benzisothiazol-3-one derivatives were modeled by quantitative structure–activity relationship (QSAR) using stepwise-multiple linear regression (SW-MLR) method. The built model was robust and predictive with correlation coefficient (R2) of 0.91 and 0.59 for training and test groups, respectively. The quality of the model was evaluated by leave-one out (LOO) cross validation (LOO correlation coefficient, Q2) of 0.80). The results indicate that the descriptors related to the electronegativity, the atomic masses, the atomic van der Waals volumes and R--CX--R Atom-centered fragments play a more significant role in caspase-3 inhibitory activity.