Quantitative Structure-Activity Relationship and Molecular Docking Study of Some Pyrrolones Antimalarial Agents against Plasmodium Falciparum

Abstract

The growing increase in multidrug resistance malaria cases necessitates the need tosearch for new cost-effective drugs. Quantitative Structure-Activity Relationship (QSAR) andmolecular docking studies were performed on a data set of forty-nine Pyrrolones antimalarial agentsagainst Plasmodium falciparum (P. falciparum). Forty-two molecules were used as a training setand seven as the test set. The molecular descriptors were obtained by Density Functional Theory(DFT) using Becke's three-parameter Lee-Yang-Parr hybrid functional (B3LYP) in combination withthe 6-31G* basis set. The QSAR model was built using Genetic Function Algorithm (GFA) method.The model with the best statistical significance (N = 42, R2ext = 0.700, R2 = 0.933, R2a = 0.916,Q2cv = 0.894, LOF = 0.417, Minimum experimental error for non-significant LOF (95%) = 0.250was selected. The docking experiment was carried out using AutoDock Vina of PyRx and DiscoveryStudio Visualizer. Docking analysis revealed that three of the studied compounds with bindingaffinity values of -10.7 kcal/mol, -10.9 kcal/mol and -11.1 kcal/mol possess higher potency thanstandard antimalarial drugs with binding affinity values of -8.8 kcal/mol, -9.5 kcal/mol and -9.0kcal/mol. It is envisioned that the wealth of information provided by the QSAR and moleculardocking results in this study will offer important structural insights for further laboratoryexperiments in the future design of novel and highly potent antimalarial from the pyrrolones.