Dihydroartemisinin-Bile Acid Hybridization as an Effective Approach to Enhance Dihydroartemisinin Anticancer Activity

ChemMedChem. 2019 Apr 3;14(7):779-787. doi: 10.1002/cmdc.201800756.

Abstract

A series of hybrid compounds based on natural products-bile acids and dihydroartemisinin-were prepared by different synthetic methodologies and investigated for their in vitro biological activity against HL-60 leukemia and HepG2 hepatocellular carcinoma cell lines. Most of these hybrids presented significantly improved antiproliferative activities with respect to dihydroartemisinin and the parent bile acid. The two most potent hybrids of the series exhibited a 10.5- and 15.4-fold increase in cytotoxic activity respect to dihydroartemisinin alone in HL-60 and HepG2 cells, respectively. Strong evidence that an ursodeoxycholic acid hybrid induced apoptosis was obtained by flow cytometric analysis and western blot analysis.

Keywords: antitumor agents; bile acids; dihydroartemisinin; hepatocellular carcinoma; natural products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Artemisinins / chemistry*
  • Artemisinins / pharmacology*
  • Bile Acids and Salts / chemistry*
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • HL-60 Cells
  • Hep G2 Cells
  • Humans
  • Inhibitory Concentration 50

Substances

  • Antineoplastic Agents
  • Artemisinins
  • Bile Acids and Salts
  • artenimol