QSAR Study of Quinazoline Derivatives as Inhibitor of Epidermal Growth Factor Receptor-Tyrosine Kinase (EGFR-TK)

摘要

Nowadays a lot of new active substances as anticancer cervix agents have been developed. One of the protein targets in discovery of anticancer cervix drugs is Epidermal Growth Factor Receptor-Tyrosine Kinase (EGFR-TK). In this present research the Quantitative Structure and Activity Relationship (QSAR) of quinazoline derivatives as inhibitors of EGFR-TK has been studied. Physicochemical parameters of quinazoline derivatives were calculated predictors to obtain the QSAR equation, and was then applied to predict the activity of new quinazoline derivatives. The best QSAR equation is IC_(50-pred) = – (3.155±19.369)~*glob + (2.280±1.291)~*mr – (0.136±0.103)~*TPSA –(1.599±2.585)~*Log P – 0.186±8.861, with n = 13, r = 0.896, r~2 = 0.803, F_(cal) = 8.152, F = 2.123, SE =1.685, Sig = 0.006, q~2 = 0.354. Based on the QSAR equation and by using the Topliss Scheme approach, three new quinazoline derivative showed higher inhibition activity than that of parent compound, and molecular docking study has shown the interaction between the those new ligand with active site of EGFR-TK.