Azole-methyl-3-(4-phenoxyphenyl) quinazolin-4(3H) ones, novel quinazoline-azole hybrid scaffolds, as new potent anticancer agents: Design, synthesis, biological evaluation, molecular dynamic simulation and theoretical approach

Herein we describe design and synthesis of new series of small quinazoline molecule connected to the azole moieties. Molecular docking screening were conducted on 102 various hybrids of quinazolinone and azole rings, toward epithelial growth factor receptor (EGFR). Among all screened compounds, six top-ranked hit hybrid scaffolds were finally selected (17a-17f), synthesized and characterized by 1HNMR, 13CNMR and Mass spectroscopy. These molecules have been tested for their antiproliferative activities against two human cancerous cell lines (MCF-7 and A549) as well as normal cell line (MRC-5). Molecular dynamic (MD) simulation were also conducted on these series to show the key drug-target interactions. The results indicated that compound 17b, harboring imidazole moiety, showed strong inhibitory activity with IC50 values of 1.38 ± 0.14 and 5.5 ± 0.09 μΜ against A549 and MCF-7 cell lines, respectively. MD simulation analysis revealed that H-bonds and hydrophobic interactions played an important role in the ligand binding stability.