Synthesis, characterization, molecular docking studies and biological evaluation of some novel hybrids based on quinazolinone, benzofuran and imidazolium moieties as potential cytotoxic and antimicrobial agents.

OBJECTIVES

Hybridization of bioactive natural and synthetic compounds is one of the most promising novel approaches for the design of hit and lead compounds with new molecular structures. In this investigation, a series of novel hybrid structures bearing quinazolinone, benzofuran and imidazolium moieties were designed and synthesized.

MATERIALS AND METHODS

Novel hybrid compounds were prepared and their structures were characterized by spectral and analytical data. In order to evaluate the biological activities, the synthesized hybrid compounds were studied for antibacterial activity against three Gram positive bacteria (, and three Gram-negative bacteria , , ) and also, as one yeast-like fungi strain. Cytotoxic activities of the synthesized compounds were also evaluated by the MTT assay in the human breast cancer cell line (MCF-7) and finally docking studies of cytotoxic derivatives were performed on aromatase enzyme.

RESULTS

The results of antimicrobial activity showed that compound 14e, with two halogen atoms on quinazolinone and benzofuran was the most active against all the tested strains of microorganisms with the MIC value 16-128 µg/ml. Some of the tested compounds showed good cytotoxicity on MCF-7, and compound 14c with IC=0.59 micromolar (μM) was found to be the most cytotoxic compound among the studied hybrid derivatives. The docking analysis showed acceptable binding interactions for these compounds.

CONCLUSION

Based on the obtained results, the hybrid derivatives of quinazolinone, benzofuran and imidazolium could be regarded as efficient candidates for further molecular developments of anticancer and antimicrobial agents.