Previous studies have suggested that
quinazolinone derivatives are potent apoptosis-inducing agents in various
cancer cell lines. In the present study, we have investigated cytotoxic, apoptosis induction, and molecular docking activities of the spiroquinazolinone
benzamide derivatives family on MCF-7 human
breast cancer cells. The MTT cytotoxicity assays and docking studies showed that 4t-CHQB was the most active compound among the prepared spiroquinazolinone
benzamide compounds with IC50 of 50 ± 1.2 μM and was selected for further assessments. Apoptosis, as the mechanism of cell death, was assessed morphologically by
acridine orange/
ethidium bromide (AO/EtBr) double staining, evaluation of the cell surface
phosphatidylserine (PS) expression through
annexin V/PI technique and, the formation of
DNA ladder. Down regulation of
survivin was evaluated in
protein level after cell treatment with 4t-CHQB using western blotting method. Molecular modeling experiments involving 4t-CHQB binding site of
survivin showed several strong hydrogen bonds and hydrophobic interactions between many important
amino acid residues. Overall, the obtained data suggest that the assessed spiroquinazolinone
benzamide compounds may provide a novel therapeutic approach for further evaluation, as an effective chemotherapeutic family acting through down regulation of
survivin and apoptosis induction in
breast cancer.