Stepwise MLR and PCR QSAR study of the pharmaceutical activities of antimalarial 3-hydroxypyridinone agents using B3LYP/6-311++G* *descriptors

Abstract

The quantitative relationship between molecular properties and pharmaceutical activities of 19 antimalarial 3-hydroxypyridinones is studied using B3LYP/6-311++G**structural, electronic, and thermochemical characteristics. In this QSAR study, stepwise-multilinear regression (MLR) and principle component regression (PCR) are utilized based on volume, HOMO, nCrH2, and nHDon descriptors selected from a number of descriptor sets calculated and examined. The MLR coefficients are evaluated by cross-validation and external test sets methods. Regression coefficients of R 2 = 0.882 and R 2 = 0.874 are obtained, respectively, for the MLR and PCR predicted pIC50 values as referenced to their experimental values. Results of PCR predict the same trend for the predicted IC50 approving validity of the MLR results. Based on the present MLR and PCR analyses, pIC50 value is calculated for six candidate antimalarial drugs designed in this work, two of which are found to have promising antimalarial activity as high as that of the two best already synthesized and examined drugs. © 2012 Springer Science+Business Media, LLC.