DFT based QSAR studies on 2-aziridinyl and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives as an anti-malarial agent

In the pursuit of better anti-malarial drugs, a quantitative structure-activity relationship (QSAR) studies have been performed on a series of 2-aziridinyl and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives. The derived QSAR model is based on three molecular descriptors namely highest occupied molecular orbital (HOMO) energy, electrophilic group frontier electron density and nucleus independent chemical shift (NICS) obtained from the density functional theory (DFT) based energy minimized and geometry optimized structures of the molecules. The best QSAR model has a square correlation coefficient q(2) = 0.900 and cross-validated square correlation coefficient. The model is also tested successfully from external validation criteria (r(pred)(2) = 0.920).