title: Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2H-chromene derivatives as potent anti-breast cancer agents.
abstract: A series of 2-aryl-3-nitro-2H-chromenes 4a-u were designed as hybrid analogs of flavanone, β-nitrostyrene and nitrovinylstilbene scaffolds. They were synthesized from the reaction of appropriate β-nitrostyrenes and salicylaldehydes in good yields. In vitro cytotoxic activities of compounds 4a-u were tested against breast cancer cell lines including MCF-7, T-47D and MDA-MB-231. Most compounds exhibited good cytotoxic activity against selected cell lines, being more potent than standard drug etoposide. Representatively, 8-methoxy-3-nitro-2-(4-chlorophenyl)-2H-chromene (4l) with IC50 = 0.2 μM against MCF-7 cells, was 36-times more potent than etoposide. Apoptosis as a mechanism of cell death for selected compounds 4h and 4l was confirmed morphologically by acridine orange/ethidium bromide double staining and TUNEL analysis, as well as caspase-3 activation assay.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Samira
authors.initials: S
authors.lastname: Rahmani-Nezhad
authors.affiliation: Department of Biotechnology, Iranian Research Organization for Science and Technology, Tehran 33535-111, Iran.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Safavi
authors.affiliation: Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Pordeli
authors.affiliation: Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran.
authors.forename: Sussan Kabudanian
authors.initials: SK
authors.lastname: Ardestani
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Khosravani
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Pourshojaei
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mahdavi
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: ashafiee@ams.ac.ir.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002839:Chromans
keywords: 2H-chromene; Anti-cancer agents; Apoptosis; Caspase-3; β-Nitrostyrene