Abstract
With a view to the rational design of a series of selected 42 substituted 1,3-diaryl propenone derivatives, quantitative structure-activity relationship (QSAR) models have been developed for the prediction of antimalarial activities against chloroquine-resistant strain of Plasmodium falciparum (W2). The statistically significant 2D-QSAR model having r2 = 0.7518 and q2 = 0.6628 with pred_r2 = 0.7189 was developed by GA-PLS and best Group based QSAR (GQSAR) model having r2 = 0.7890 and q2 = 0.7043 with pred_r2 = 0.7297 was developed by SW-MLR method. The three-point pharmacophore hypothesis yielded a 3D-QSAR model with good PLS statistics results (r2 = 0.985, Q2 ext = 0.967, F = 312.7, rpret 2 = 0.969, SD = 0.059, RMSE = 0.083, Pearson-R = 0.996). The results of 2D-QSAR, GQSAR and atom-based 3D-QSAR studies give detailed structural insights as well as highlights important binding features of these substituted 1,3-diaryl propenone derivatives as antimalarial agents which can provide guidance for the rational design of novel potent P. falciparum growth inhibitors.
Keywords: Antimalarial agents, Chalcones, 1,3-Diaryl Propenone, QSAR, VLife MDS, Pharmacophore, Plasmodium falciparum, chloroquine-resistant, enzyme targets, pharmacophore box, Schrodinger suite, Chalcone, Merck Molecular Force Field, potential antimalarial activity, randomization, AveragePotential
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