3D-QSAR Analysis of Some Cinnamic Acid Derivatives as Antimalarial Agents

Abstract

A set of sixteen cinnamic acid derivatives with antiprotozoan activity against Plasmodium falciparum was subjected to the three dimensional quantitative structure activity relationship studies using various combinations of thermodynamic, electronic and spatial descriptors. Among several 3D quantitative structure activity relationship models, one model gave good statistical significance (r > 0.83, F-test = 9.47, S < 0.33, chance correlation < 0.01 and cross validated r² > 0.43) involving the descriptors, viz., van der Waals' 1,4 energy, energy of lowest unoccupied molecular orbital and principal moment of inertia of xcomponent. The predictive power of this model was discerned by successfully testing the four compounds constituting the test set with predictive r² > 0.61. Thus, this validated model brings important structural insight to aid the design of novel antimalarial agents.