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: Gurleen Kaur, Mohinder P Mahajan, Manoj K Pandey, Parvesh Singh, Srinivasa R Ramisetti, Arun K Sharma
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 86 Pg. 211-8 (Oct 30 2014) ISSN: 1768-3254 [Electronic] France
• PMID: 25164760 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Tamoxifen
• Ospemifene

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Design
• Drug Screening Assays, Antitumor
• Humans
• MCF-7 Cells
• Models, Molecular
• Molecular Structure
• Structure-Activity Relationship
• Tamoxifen (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Tumor Cells, Cultured