QSAR analysis of novel N-alkyl substituted isatins derivatives as anticancer agents

Raj K. Prasada, Tamanna Narsin

Abstract

A set of twenty N-alkyl substituted isatins derivatives with anticancer activity was subjected to the two dimensional quantitative structure activity relationships (2D-QSAR) studies using MDS 3.0 drug designing module with various combinations of thermodynamic, electronic and spatial descriptors. N-alkylation’s of isatin derivatives taken as the lead molecule and QSAR model developed using different multiple regression approach. Logarithmic inverse value of IC-50 was taken as dependent variable and Bromines Count, chi2 and SA Hydrophilic Area was taken as independent variable. The best QSAR model (r2 = 0.92, Fisher test value F=42.72, r2 se = 0.14) has acceptable statistical quality and predictive potential as indicated by the value of cross validated squared correlation coefficient (q2= 0.84). From the build model it seems to be clear that Bromines Count, chi2 and SA Hydrophilic Area contribute negative biological activity. Thus this validated model brings important structural insight to aid the design of novel antimycobacterial agents