QSAR analysis of 7-substituted 4-aminoquinolines as antimalarial agents

The emergence and rapid spread of chloroquine resistant strains of Plasmodium falciparum has dramatically reduced the chemotherapeutic options. Towards this goal, the quantitative structure-activity relationship analysis of some synthesized 7-substituted 4aminoquinolines were performed for their antiplasmodial activity against chloroquine-resistant parasites to find out the structural features responsible for the biological activity. The statistically significant best 2D QSAR model having correlation coefficient (r) = 0.8631 and cross validated squared correlation coefficient (q) = 0.8101 with external predictive ability (pred_r) = 0.6740 was developed by Partial Least Square Regression coupled with stepwise backward-forward method using Vlife MDS 3.5 software and showed that the parameters Average-vePotential, T_2_N_5, XcompDipole and QMDipoleX are highly correlated with antiplasmodial activity of 7-substituted 4-aminoquinolines. The developed models are interpretable, with good statistical and predictive significance, and can be used for guiding ligand modification for the development of potential new amtimalarial agents.