Synthesis and cytotoxic activity of novel 1-((indol-3-yl)methyl)-1H-imidazolium salts

Bioorg Med Chem Lett. 2014 Nov 1;24(21):4926-30. doi: 10.1016/j.bmcl.2014.09.045. Epub 2014 Sep 23.

Abstract

A series of novel 1-((indol-3-yl)methyl)-1H-imidazolium salts were prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the 5,6-dimethyl-benzimidazole ring, and substitution of the imidazolyl-3-position with a naphthylacyl or 4-bromophenacyl group, were vital for modulating inhibitory activity of cell growth. In particular, 1-((N-Boc-indol-3-yl)methyl)-3-(2-naphthylacyl)-1H-5,6-dimethyl-benzimidazolium bromide was found to be the most potent derivative and more selective against myeloid liver carcinoma (SMMC-7721), lung carcinoma (A549) and breast carcinoma (MCF-7), with IC50 values 1.9-fold, 1.7-fold and 4.8-fold lower than DDP. This compound can induce significant cell apoptosis in SMMC-7721 cells.

Keywords: Cell apoptosis; Imidazolium salts; Indole; Structure–activity relationships.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Imidazoles