METAPHORICAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP (2D & 3D-QSAR) ANALYSIS OF TYLOPHORINE DERIVATIVES AS EFFICACIOUS IN ANTIMALARIAL DRUG DESIGNAbstract
Quantitative Structure-Activity Relationship (QSAR) for tylophorine derivatives acting as Plasmodium kinases inhibitors has been developed. The proposed 2D-QSAR model was found to be statistically significant concerning training, cross-validation, and external validation. The contribution of carbon chains with aromatic and electronegative features are found to be the most important descriptors in predicting Plasmodium kinases inhibitory activity. Furthermore, a 3D-QSAR study using CoMFA and CoMSIA was carried out to investigate the molecular property determinants. The CoMFA model suggested that the favorable substitution of steric groups with electronegative properties at ring A. Furthermore, CoMSIA model indicated the possible role of H bond donor groups at 5 and 6 positions of ring A whereas H bond acceptors at 7 and 8 positions of ring A in enhancing the biological activities. The developed QSAR models can be used to discover new effective antimalarial leads for further development as antimalarial drugs.
S. K. Patel, L. George, V. M. Khedkar, M. Y. Lone, P. C. Jha *, Y. T. Jasrai, H. A. Pandya and H. N. Highland
School of Chemical Sciences, Central University of Gujarat, Gandhinagar, Gujarat, India.
26 March 2014
15 May 2014
12 July 2014
01 October 2014