Synthesis of novel ring-A fused hybrids of oleanolic acid with capabilities to arrest cell cycle and induce apoptosis in breast cancer cells

Eur J Med Chem. 2014 Mar 3:74:398-404. doi: 10.1016/j.ejmech.2013.12.040. Epub 2014 Jan 8.

Abstract

Six novel oleanolic acid ring-A fused hybrids (5-10) have been synthesized by employing a four step protocol with the introduction of benzylidene functionality at C-2 as the key step. Their structures were established by high resolution NMR and Mass spectral data. The synthesized compounds have been screened against seven human cancer cell lines including ME-180 & HeLa (cervix), MCF-7, MDA-MB-453 & MDA-MB-231 (breast), PC-3 (prostate) and HT-29 (colon) using MTT assay. Most significantly, compound 10 showed potent activity against the three breast cancer cell lines. The IC₅₀ value (10.60 μM) of compound 10 against MCF-7 found to be much lower than that of the standards and parent compound. Flow cytometric analysis reveals that compound 10 arrests cell cycle in S phase and induces apoptosis in MCF cells.

Keywords: Anti-cancer activity; Apoptosis; Cell cycle arrest; Oleanolic acid; Oleanolic acid hybrids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Breast Neoplasms / pathology*
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Oleanolic Acid / chemical synthesis
  • Oleanolic Acid / chemistry*
  • Oleanolic Acid / pharmacology

Substances

  • Oleanolic Acid