Abstract
Quantitative structure activity relationship (QSAR) model for antimalarial activity was developed from a set of 51 substituted quinazolines that exhibited remarkable in vitro activity against sensitive and multidrug-resistant Plasmodium falciparum malaria. 2D-QSAR was done using partial least squares method coupled with stepwise variable selection; subsequently, 3D-QSAR was carried out using stepwise variable selection k-nearest neighbor molecular field analysis (kNNMF) approach. Leave-one-out cross-validated correlation coefficient (q 2) of 0.7601 and a predicted r 2 for the external test (pred_r 2) of 0.7108 were obtained with 3D QSAR. Experimental results revealed that the molecular weight, alignment-independent descriptors, electrostatic and steric field descriptors were significantly correlated with antimalarial activity of quinazoline derivatives. The results helped to understand the nature of substituents around quinazoline nucleus, thereby providing new guidelines for the design of novel antimalarials.
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The author is grateful to Head, Department of Pharmacy, Barkatullah University, Bhopal, for providing the V-Life MDS software Version 3.5 and other necessary facilities for carrying out the Research.
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Mishra, M., Mishra, V.K., Senger, P. et al. Exploring QSAR studies on 4-substituted quinazoline derivatives as antimalarial compounds for the development of predictive models. Med Chem Res 23, 1397–1405 (2014). https://doi.org/10.1007/s00044-013-0744-8
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DOI: https://doi.org/10.1007/s00044-013-0744-8