2. Academic Validation
  3. Design, synthesis, and anti-breast cancer evaluation of new triarylethylene analogs bearing short alkyl- and polar amino-/amido-ethyl chains

Design, synthesis, and anti-breast cancer evaluation of new triarylethylene analogs bearing short alkyl- and polar amino-/amido-ethyl chains

  • Bioorg Med Chem Lett. 2016 Apr 15;26(8):1963-9. doi: 10.1016/j.bmcl.2016.03.008.
Gurleen Kaur 1,  Mohinder P Mahajan 2,  Manoj K Pandey 3,  Parvesh Singh 4,  Srinivasa R Ramisetti 3,  Arun K Sharma 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Apeejay Stya University, Plot No. 23, Institutional Area, Sector-32, Gurgaon 122001, India.
  • 2 School of Pharmaceutical Sciences, Apeejay Stya University, Plot No. 23, Institutional Area, Sector-32, Gurgaon 122001, India. Electronic address: mahajanmohinderp@yahoo.co.in.
  • 3 Department of Pharmacology, Penn State Hershey Cancer Institute, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, United States.
  • 4 School of Chemistry and Physics, University of Kwa-Zulu Natal (UKZN), Westville Campus, Durban 4000, South Africa.
PMID: 26972118 DOI: 10.1016/j.bmcl.2016.03.008
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.

Keywords

Anti-breast cancer drugs; Molecular docking; Ospemifene; SERMs; Tamoxifen.

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