6‐Bromoquinazoline Derivatives as Potent Anticancer Agents: Synthesis, Cytotoxic Evaluation, and Computational Studies

Abstract

A series of 6-bromoquinazoline derivatives (5a-j) were synthesized. Cytotoxic effectiveness of compounds was done against two cancerous cell lines (MCF-7 and SW480) by standard MTT method. Fortunately, all of the compounds showed desirable activity in reducing the viability of the studied cancerous cell lines with IC 50 value in the range of 0.53-46.6 μM. Compound 5b with a fluoro substitution at meta position of the phenyl moiety showed stronger activity than cisplatin with IC 50 = 0.53-1.95 μM. Studies on the hit compound (5b) through apoptosis assay illustrated that it could induce apoptosis in MCF-7 cell lines in dose dependent manner. Molecular docking study was done to investigate the detailed binding modes and interactions with EGFR as a plausible mechanism. The drug-likeness was predicted. To survey the reactivity of compounds, DFT calculation was performed. Taken together, 6-bromoquinazoline derivatives, especially 5b can be considered as hit compounds to rational drug designing as antiproliferative agents.