2-(Chloromethyl)-3-phenylquinazolin-4(3H)-ones as potent anticancer agents; cytotoxicity, molecular docking and in silico studies

In order to show antiproliferation and cancerous cell growth inhibition of quinazoline derivatives, a series of 2-(chloromethyl)-3-phenylquinazolin-4(3H)-ones (H-1-H-11) were synthesized. In vitro cytotoxic activities were evaluated against three human cancer cell lines: A549, MCF-7 and SW1116 using colorimetric MTT assay. Comparing their effects together and with cisplatin as a positive control indicated that H-3, H-5 and H-6 exhibited better antitumor activities on A549 cell line with IC50 values less than 10 mu M versus 12 mu M for cisplatin. In the case of MCF-7 and SW1116 cell lines, almost all compounds displayed better cytotoxic activities than cisplatin. Molecular docking studies were applied on epidermal growth factor receptor (EGFR) as the main target of quinazoline scaffolds in cancer therapy to predict the binding energies, binding modes and orientation of these ligands toward the active site of the receptor. In silico physicochemical parameters and ADMET profiling calculations also were done. All compounds showed lower binding energies than erlotinib, the inhibitor of EGFR. Taken together, our findings showed potential anticancer effect of quinazoline compounds bearing various phenyl ring substitutions. [GRAPHICS] .

Automated summary

A series of quinazoline derivatives were synthesized to demonstrate their antiproliferative and antitumor activities against human cancer cell lines. Some compounds showed better cytotoxic effects than cisplatin in vitro, with molecular docking studies indicating strong binding to EGFR. These findings suggest the potential anticancer effects of quinazoline compounds with phenyl ring substitutions.