Design, synthesis and evaluation of Ospemifene analogs as anti-breast cancer agents
European Journal of Medicinal Chemistry
School of Pharmaceutical Sciences, Apeejay Stya University, Institutional Area, Gurgaon 122001, India; Apeejay Stya Research Foundation, Institutional Area, Gurgaon 122001, India; Department of Pharmacology, Penn State Hershey Cancer Institute, CH72 Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, United States; School of Chemistry and Physics, University of Kwa-Zulu Natal (UKZN), Westville Campus, Durban 4000, South Africa
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. © 2014 Elsevier Masson SAS. All rights reserved.
2 [ 4 ( 4 amino 1,2 diphenylbut 1 enyl)phenoxy]ethanol; 2 [ 4 ( 4 azido 1,2 diphenylbut 1 enyl)phenoxy]ethanol; 4 [ 4 ( 2 aminoethoxy)phenyl] 3,4 diphenylbut 3 en 1 amine; antineoplastic agent; estrogen receptor; estrogen receptor alpha; estrogen receptor beta; hormone receptor stimulating agent; ospemifene; ospemifene derivative; phenyl 4 [ 4 ( 2 hydroxyethoxy)phenyl] 3,4 diphenylbut 3 enylcarbamic acid; selective estrogen receptor modulator; tamoxifen; unclassified drug; 2 [4 (4 amino1,2 diphenylbut 1 enyl) phenoxy]ethanol; 2 [4 (4 azido 1,2 diphenylbut 1 enyl)phenoxy]ethanol; 2 [4 (4 chloro 1,2 diphenylbut 1 enyl) phenoxy]ethanol; 2 [4 (4 chloro 1,2 diphenylbut 1 enyl)phenoxy]ethyl methanesulfonate; 4 [4 (2 aminoethoxy)phenyl] 3,4 diphenylbut 3 en 1 amine; antineoplastic agent; ospemifene; ospemifene derivative; phenyl 4 [4 (2 hydroxyethoxy)phenyl] 3,4 diphenylbut 3 enylcarbamate; selective estrogen receptor modulator; tamoxifen; [1 [4 (2 azidoethoxy) phenyl] 4 chlorobut 1 ene 1,2 diyl]dibenzene; [4 azido 1 [4 (2 azidoethoxy)phenyl]but 1 ene 1,2 diyl]dibenzene; antineoplastic agent; ospemifene; antineoplastic activity; article; binding affinity; breast cancer cell line; cell viability; controlled study; cytotoxicity; drug design; drug potency; drug protein binding; drug synthesis; growth inhibition; human; human cell; IC 50; MCF 7 cell line; molecular docking; animal cell; antineoplastic activity; Article; breast cancer; cancer inhibition; concentration response; drug cytotoxicity; drug screening; drug selectivity; embryo; IC50; mouse; nonhuman; analogs and derivatives; Breast Neoplasms; cell proliferation; cell survival; chemical structure; chemistry; dose response; drug effects; drug screening; pathology; structure activity relation; synthesis; tumor cell culture; Antineoplastic Agents; Breast Neoplasms; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Humans; MCF-7 Cells; Models, Molecular; Molecular Structure; Structure-Activity Relationship; Tamoxifen; Tumor Cells, Cultured