Drug discovery studies on quinoline-based derivatives as potential antimalarial agents

SAR and QSAR in Environmental Research
R SharmaP Maurya

Abstract

Molecular modelling studies were performed to identify the essential structural requirements of quinoline-based derivatives for improving their antimalarial activity. The developed CoMFA, CoMSIA and HQSAR models for a training set comprising 37 derivatives showed good statistical significance in terms of internal cross validation (q(2)) 0.70, 0.69 and 0.80 and non-cross validation (r(2)) 0.80, 0.79 and 0.80. Also, the predicted r(2) values (r(2)pred) of 0.63, 0.61 and 0.72 for a test set consisting of 12 compounds suggested significant predicting ability of the models. Structural features were correlated in terms of steric, electrostatic, hydrophobic, hydrogen bond donor and hydrogen bond acceptor interactions. Furthermore, the bioactive conformation was explored and explained by docking compounds #28, 32 and 40 into the active binding site of lactate dehydrogenase of Plasmodium falciparum. The QSAR models, contour map and docking binding affinity obtained could be successfully utilized as a guiding tool for the design and discovery of novel quinoline-based derivatives with potent antimalarial activity.

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Citations

Nov 3, 2015·SAR and QSAR in Environmental Research·J Sainy, R Sharma
May 30, 2014·Journal of Biomolecular Structure & Dynamics·Mahalakshmi ThillainayagamSudha Ramaiah
Aug 25, 2020·Materials Today : Proceedings·M ChandrappaPhani Kumar Pullela

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Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.