Metaphorical Quantitative Structure-activity Relationship (2d & 3d- Qsar) Analysis of Tylophorine Derivatives as Efficacious in Antimalarial Drug Design

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 with respect to 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, 3D-QSAR study using CoMFA and CoMSIA was carried out to investigate the molecular property determinants. The CoMFA model suggested that the favourable 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. INTRODUCTION: The extended focus of the malaria society on eradication of this disease has arisen both in responses to the moral imperative to save lives and eliminate the devastating disease burden and in recognition that a pure casemanagement approach is unsustainable 1 . QUICK RESPONSE CODE DOI: 10.13040/IJPSR.0975-8232.5(10).4325-38 Article can be accessed online on: www.ijpsr.com DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.5(10).4325-38 Thus renewed efforts are being made to develop insecticides that overcome known resistance pathways and kill all mosquitos, to deliver vaccines that protect infants and children and to discover, develop and deliver medicines that not only clear the asexual blood stage parasites but also the asymptomatic forms (exo-eryothrocytic stages) that secure the lifecycle of Plasmodium 2 . Malaria is an infectious disease caused by plasmodium species, transmitted through anopheles mosquitoes, a severe disease that still caused about 225 million cases and 781,000 human deaths. The plasmodium affects the human red blood cells and damages them over the