Dihydroartemisinin-bile acid hybridization as an effective approach to enhance dihydroartemisinin anticancer activity

A series of hybrid compounds based on natural products bile acids and dihydroartemisinin (DHA) 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 synthesized hybrids presented significantly improved antiproliferative activities respect to DHA and parent bile acids. Compounds 2 and 13 were the most potent hybrids of the series with a 10.5- and 15.4-fold increase in cytotoxic activity respect to DHA alone in HL-60 and HepG2 cells, respectively. Strong evidence that hybrid 2 induced apoptosis was obtained by flow cytometric analysis as well as Western blot analysis.