Design, synthesis and in vitro cytotoxicity studies of novel β-carbolinium bromides

Bioorg Med Chem Lett. 2017 Mar 15;27(6):1379-1384. doi: 10.1016/j.bmcl.2017.02.010. Epub 2017 Feb 9.

Abstract

A series of novel β-carbolinium bromides has been synthesized from easily accessible β-carbolines and 1-aryl-2-bromoethanones. The newly synthesized compounds were evaluated for their in vitro anticancer activity. Among the synthesized derivatives, compounds 16l, 16o and 16s exhibited potent anticancer activity with IC50 values of <10μM against tested cancer cell lines. The most potent analogue 16l was broadly active against all the tested cancer cell lines (IC50=3.16-7.93μM). In order to test the mechanism of cell death, we exposed castration resistant prostate cancer cell line (C4-2) to compounds 16l and 16s, which resulted in increased levels of cleaved PARP1 and AO/EB staining, indicating that β-carbolinium salts induce apoptosis in these cells. Additionally, the most potent β-carbolines 16l and 16s were found to inhibit tubulin polymerization.

Keywords: Apoptosis; In vitro cytotoxicity; Microwave; β-Carbolinium bromides.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bromides / chemical synthesis*
  • Bromides / chemistry
  • Bromides / pharmacology*
  • Carbolines / chemical synthesis*
  • Carbolines / chemistry
  • Carbolines / pharmacology*
  • Cell Line, Tumor
  • Drug Design
  • Humans
  • Male
  • Prostatic Neoplasms / pathology

Substances

  • Bromides
  • Carbolines