title: Design, synthesis and evaluation of Ospemifene analogs as anti-breast cancer agents.
abstract: The synthesis of some novel Ospemifene derived analogs and their evaluation as anti-breast cancer agents against MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) human breast cancer cell lines are described. Few of these analogs for instance, compounds 6, 7 and 8 are shown to be more effective than recent Selective Estrogen Receptor Modulators (SERMs) i.e. Ospemifene and Tamoxifen, against these cell lines. Compound 8 was relatively more cytotoxic to MCF-7 cells similar to Ospemifene and Tamoxifen, while most potent compounds 6 and 7 were equally effective in inhibiting growth of both ER-positive and ER-negative cell lines. The observed activity profiles were further supported by the docking studies performed against estrogen receptors (ERα and ERβ). Compounds 6, 7 and 8 exhibited stronger binding affinities with both ERα and ERβ compared to Ospemifene and Tamoxifen.
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; Apeejay Stya Research Foundation, Plot No. 23, Institutional Area, Sector-32, Gurgaon 122001, India. Electronic address: mpmahajan@apeejay.com.
authors.forename: Mohinder P
authors.initials: MP
authors.lastname: Mahajan
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, CH72 Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
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, CH72 Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Ramisetti
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, CH72 Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Sharma
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D013629:Tamoxifen; C119141:Ospemifene
keywords: Anti-breast cancer agents; Docking studies; Ospemifene; SERMs; Tamoxifen