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

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 IC50 value in the range of 0.53-46.6 mu M. Compound 5b with a fluoro substitution at meta position of the phenyl moiety showed stronger activity than cisplatin with IC50=0.53-1.95 mu M. 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.

Automated summary

A series of 6-bromoquinazoline derivatives were synthesized and their cytotoxic effectiveness against two cancerous cell lines was evaluated. All compounds showed desirable activity in reducing cell viability, with IC50 values ranging from 0.53 to 46.6 μM. Compound 5b, with a fluoro substitution at meta position of the phenyl moiety, exhibited stronger activity than cisplatin. Further studies revealed that compound 5b induced apoptosis in a dose-dependent manner and interacted with EGFR through molecular docking.