Журнал протеомики и биоинформатики
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In-silico Interaction Studies of Quinazoline Derivatives for their Inhibitory Action on Both Wild and Mutant EGFRs

Kaushik S. Hatti, V. Chandregowda, G.Venkateswara Rao, Anil Kush and G.Chandrasekara Reddy

Epidermal growth factor receptor (EGFR) family has gained importance as a target for cancer therapy. However, somatic mutations in the tyrosine kinase domain of EGFR alter its sensitivity to anti-EGFR tyrosine kinase (TK) drugs like gefitinib (IressaTM). Docking studies of a few newly synthesized 6, 7-dialkoxy-4-anilinoquinazoline derivatives which showed EGFR-TK inhibitory activity were conducted. It has been found that the docking energies of these novel quniazolines are comparable with the IC50 values against A431 and MCF-7 tumor cell lines. Though the compounds with benzoxazole (1 & 2) and imidazole side chain (4) exhibited low binding energy to wild-type, but compound 3 had the lowest binding energy to its mutants as well (T790M, L858R and double-mutant). Compounds 1, 2, 4 and gefitinib showed affinity only for selective EGFR variants.