Synthesis, Characterization, DFT Studies, Biological Investigation and Molecular Modelling of Novel 1-(5-(1H-imidazol-1-yl)-3-methyl-1-phenyl-1H-pyrazol-4-yl)- 3-amino-2-cyano-N-phenyl-1H-benzo[f]chromene-5-carboxamide Derivatives

Abstract

In this work, a new series of imidazole-pyrazole-benzo[f]chromene hybrids were designed and synthesized by a base-catalyzed cyclo-condensation through a one-pot multicomponent reaction. All compounds were tested for in vitro antimicrobial and anticancer activities. Enzyme inhibitory activities of all compounds were carried out against FabH and EGFR. The majority of synthesized  compounds displayed promising antimicrobial as well as anticancer activity against used strains and cancer cell lines respectively. The  compounds were also tested for in vitro anticancer activities against two cancer cell lines A549 and Hep G2. Compound 7f (IC50 = 0.62  µM) against EGFR and (IC50 = 1.31 µM) against A549 kinase displayed the most potent inhibitory activity as compared to another  member of the series. In the molecular modelling study, compound 7e was bound into the active pocket of EGFR with one pi-pi  interaction and one hydrogen bond having minimum binding energy ∆Gb = −7.6894 kcal/mol. Moreover, FabH molecule 7d was found  to be binding in the active pocket with a minimum binding energy of −8.9117 kcal/mol.