title: Evaluation of the cytotoxic, apoptosis inducing activity and molecular docking of spiroquinazolinone benzamide derivatives in MCF-7 breast cancer cells.
abstract: 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.
authors.affiliation: Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran. Electronic address: majid.mahdavi@tabrizu.ac.ir.
authors.forename: Majid
authors.initials: M
authors.lastname: Mahdavi
authors.affiliation: Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.
authors.forename: Malihe Mohseni
authors.initials: MM
authors.lastname: Lavi
authors.affiliation: Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Yekta
authors.affiliation: Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Moosavi
authors.affiliation: Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Nobarani
authors.affiliation: Department of Chemistry, Faculty of Science, K. N. Toosi University of Tech, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Balalaei
authors.affiliation: Pharmaceutical Biotechnology Department, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Sanam
authors.initials: S
authors.lastname: Arami
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Rashidi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008024:Ligands; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology*; D000077022:Survivin; D013816:Thermodynamics
chemical_list: C107489:BIRC5 protein, human; D001549:Benzamides; D051034:Inhibitor of Apoptosis Proteins; D008024:Ligands; D013141:Spiro Compounds; D000077022:Survivin; C088106:spiroquinazoline; C037689:benzamide
keywords: Apoptosis; MCF-7 cells; Spiroquinazolinone benzamide; Survivin