Design synthesis and pharmacological evaluation of novel quinazoline derivatives as potential anticancer agents

Abstract

The current study involves design, synthesis and biological study of the novel quinazoline derivatives as anticancer agents. Various 4,6,7-trisubstituted 4-anilino and 4-aryloxy quinazoline derivatives were prepared. The structures of the newly synthesized compounds were confirmed by various analytical techniques such as IR, 1H, 13C NMR spectroscopy and mass spectrometry. The newly synthesized quinazoline analogues were screened against a panel of cancer cell lines at preliminary dose of 10 and#956;M. Several gefitinib based 4,6,7- trisubstituted quinazolines displayed enhanced and selective antiproliferative activity against several solid tumor cell lines such as NCI-H322M, NCI-H522 (non-small cell lung cancer), IGROV1, SK-OV-3 (ovarian cancer), TK-10 (renal cancer) and MDA-MB-468 (breast cancer). A series of quinazoline derivatives were also studied for EGFR kinase inhibition and subsequently the potent ones were also analysed using western blot assay to gain mechanistic insights. Molecular docking to study the receptor-ligand interactions was also performed. Several quinazoline analogues displayed activities comparable to reference drugs. The outcome of the present research work would further help in developing potent quinazoline based cytotoxic compounds. newline