Journal of Chemical and Pharmaceutical Research (ISSN : 0975-7384)

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Original Articles: 2017 Vol: 9 Issue: 5

A Molecular Modelling Study on Derivatives of Pyrazolyl Thiazolinone as Potential EGFR and HER-2 Kinase Inhibitors

Abstract

EGFR and HER-2 kinase are protein tyrosine kinase receptors (PTKRs) also called Phosphotyrosinkinase receptors play significant role in controlling cell division and differentiation step in cell-cycle. It is also a promising strategy for the development of novel and newer anticancer agents. In pursuit of better anticancer agents, pyrazolyl thiazolinone derivatives were quantitatively studied by using Fujita ban, Hansch and 3D-QSAR analysis. Sequential multiple linear regression analysis was used for building the QSAR model. The QSAR model was generated using 24 compounds as training set. Developed QSAR model was internally validated using leave-one-out method of cross-validation (q2) and externally validated using test set considering predictive squared correlation coefficient (Pred-r2). Molecular modelling and QSAR analysis revealed that electronic and steric parameters contribute significantly to its inhibitory activity. Substitution by the methyl group at R1 position increase the lipophilicity and R2 position remain unsubstituted or substituted with bromine group is more favourable for kinase inhibitory activity, whereas substitution at R1 position with more electronegative group contributed negatively. The results of present study may be useful in designing of newer, more potent and more active pyrazolyl-thiazolinone analogs as EGFR and HER-2 kinase inhibitors.