title: Design, synthesis, and anti-breast cancer evaluation of new triarylethylene analogs bearing short alkyl- and polar amino-/amido-ethyl chains.
abstract: The synthesis of novel triarylethylene analogs, designed based on well-known Selective Estrogen Receptor Modulators (SERMs), i.e., ospemifene and tamoxifen, as potential anti-breast cancer agents is described. The cytotoxic potential of these analogs against ER-positive (MCF-7) and ER-negative (MDA-MB-231) human breast cancer cell lines was determined and compared with the standards, ospemifene and tamoxifen. In initial screening, analogs 5, 14 and 15 were found to be much more effective than the standards against both the cell lines. The results showed that these novel analogs inhibit the expression of proteins involved in the migration and metastasis, compound 5 being most effective. Compound 5 inhibited the expression of MMP-9, c-Myc and Caveolin in both MCF-7 and MDA-MB-231 cells, and suppressed the invasion of ER-negative cells in a dose dependent manner. Finally, in silico docking simulations of the representative compounds in the binding sites of the estrogen receptors (ERs) indicated a good binding affinity of the compounds with the ERs, and supported their experimental toxicity against MCF-7 cancer cell lines.
authors.affiliation: School of Pharmaceutical Sciences, Apeejay Stya University, Plot No. 23, Institutional Area, Sector-32, Gurgaon 122001, India.
authors.forename: Gurleen
authors.initials: G
authors.lastname: Kaur
authors.affiliation: School of Pharmaceutical Sciences, Apeejay Stya University, Plot No. 23, Institutional Area, Sector-32, Gurgaon 122001, India. Electronic address: mahajanmohinderp@yahoo.co.in.
authors.forename: Mohinder P
authors.initials: MP
authors.lastname: Mahajan
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Pandey
authors.affiliation: School of Chemistry and Physics, University of Kwa-Zulu Natal (UKZN), Westville Campus, Durban 4000, South Africa.
authors.forename: Parvesh
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Ramisetti
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Sharma
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005030:Ethylenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000588:Amines; D000970:Antineoplastic Agents; D005030:Ethylenes; D011960:Receptors, Estrogen
keywords: Anti-breast cancer drugs; Molecular docking; Ospemifene; SERMs; Tamoxifen