Dihydroartemisinin–Bile Acid Hybridization as an Effective Approach to Enhance Dihydroartemisinin Anticancer Activity. (4th April 2019)

• Record Type: Journal Article
• Authors: Marchesi, Elena; Chinaglia, Nicola; Capobianco, Massimo L.; Marchetti, Paolo; Huang, Tzu‐En; Weng, Hao‐Cheng; Guh, Jih‐Hwa; Hsu, Lih‐Ching; Perrone, Daniela; Navacchia, Maria Luisa
• Is Part Of: ChemMedChem. Volume 14:Number 7(2019)
• Page Start: 779
• Page End: 787
• Publication Date: 2019-04-04
• Subjects: antitumor agents -- bile acids -- dihydroartemisinin -- hepatocellular carcinoma -- natural products; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201800756
• Languages: English
• ISSNs: 1860-7179

Abstract

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. Abstract : Conjugate killers : A new series of hybrids integrating two natural molecules—dihydroartemisinin and a selected bile acid—were prepared through highly stereoselective one‐pot reactions. The efficiency of the hybrid approach was demonstrated by the enhanced cytotoxicity and cytoselectivity of the hybrids with respect to the parent molecules alone. The biological study was focused on the HL‐60 leukemia and HepG2 hepatocellular carcinoma cell lines.