Design, synthesis and biological evaluation of β-boswellic acid based HDAC inhibitors as inducers of cancer cell death

Bioorg Med Chem Lett. 2014 Oct 1;24(19):4729-4734. doi: 10.1016/j.bmcl.2014.08.007. Epub 2014 Aug 14.

Abstract

The synthesis and bio-evaluation of naturally occurring boswellic acids (BAs) as an alternate CAP for the design of new HDAC inhibitors is described. All the compounds were screened against a panel of human cancer cell lines to identify leads, which were subsequently examined for their potential to inhibit HDACs. The identified lead compound showed IC50 value of 6μm for HDACs, found to induce G1 cell cycle arrest at significantly low concentration (1μM) and caused significant loss in mitochondrial membrane potential at 5 and 10μM. Furthermore, specific interactions of the lead molecule inside the catalytic domain were also studied through in silico molecular modeling.

Keywords: Anti-cancer; HDAC; Hydroxamic acid; β-Boswellic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • HCT116 Cells
  • HL-60 Cells
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism*
  • Humans
  • MCF-7 Cells
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Triterpenes
  • boswellic acid
  • Histone Deacetylases