Bismuth nitrate-induced novel nitration of estradiol: An entry to new anticancer agents

Debasish Bandyopadhyay, Gildardo Rivera, Jorge L. Sanchez, Jesse Rivera, Jose C. Granados, Adrian M. Guerrero, Fang Mei Chang, Robert K. Dearth, John D. Short, Bimal K. Banik

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Direct nitration of estradiol was carried out using metal nitrates on solid surfaces under mild condition, and a combination of bismuth nitrate pentahydrate impregnated KSF clay was found to be the best reagent to synthesize 2- and 4-nitroestradiol effectively. Furthermore, various basic side chains were introduced, through O-linker at C-3, to these nitroestradiols. The ability of these derivatives to cause cytotoxicity in Estrogen Receptor (ER)-positive and ER-negative breast cancer cell lines, as well as cancer cell lines of other origins, was examined. Qualitative structure activity relationship (SAR) has also been studied. We found that a basic side chain containing either a piperidine or morpholine ring, when conjugated to 2-nitroestradiol, was particularly effective at causing cytotoxicity in each of the cancer cell lines examined. Surprisingly, this effective cytotoxicity was even seen in ER-negative breast cancer cells.

Original languageEnglish (US)
Pages (from-to)574-583
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
Volume82
DOIs
StatePublished - Jul 23 2014

Keywords

  • Anticancer
  • Apoptosis
  • Bismuth nitrate
  • Estradiol
  • Estrogen receptor
  • Nitration
  • Solid-support

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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    Bandyopadhyay, D., Rivera, G., Sanchez, J. L., Rivera, J., Granados, J. C., Guerrero, A. M., Chang, F. M., Dearth, R. K., Short, J. D., & Banik, B. K. (2014). Bismuth nitrate-induced novel nitration of estradiol: An entry to new anticancer agents. European Journal of Medicinal Chemistry, 82, 574-583. https://doi.org/10.1016/j.ejmech.2014.06.010