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Dihydroartemisinin–Bile Acid Hybridization as an Effective Approach to Enhance Dihydroartemisinin Anticancer Activity
Author(s) -
Marchesi Elena,
Chinaglia Nicola,
Capobianco Massimo L.,
Marchetti Paolo,
Huang TzuEn,
Weng HaoCheng,
Guh JihHwa,
Hsu LihChing,
Perrone Daniela,
Navacchia Maria Luisa
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800756
Subject(s) - dihydroartemisinin , ursodeoxycholic acid , chemistry , in vitro , pharmacology , bile acid , hepatocellular carcinoma , artemisinin , biology , biochemistry , cancer research , immunology , plasmodium falciparum , malaria
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.