Synthesis of a series of novel dihydroartemisinin monomers and dimers containing chalcone as a linker and their anticancer activity

• New artemisinin-chalcone hybrids were synthesized.
• Hybrids investigated for cytotoxicity in four human cancer cell lines.
• Most potent compounds 8 with IC50 = 0.3 μM against HL-60.
• Compound 8 is six times active than DHA (with IC50 = 2 μM).

A new series of monomer and dimer derivatives of dihydroartemisinin (DHA) containing substituted chalcones as a linker were synthesized and investigated for their cytotoxicity in human cancer cell lines HL-60 (leukemia), Mia PaCa-2 (pancreatic cancer), PC-3 (prostate cancer), LS180 (colon cancer) and HEPG2 (hepatocellular carcinoma). Some of these derivatives have greater antiproliferative and cytotoxic effects in tested cell lines than parent compound DHA. The structures of the all compounds were confirmed by IR, 1H NMR and mass spectral data. Among the new derivatives, compounds 8, 14, 15, 20 and 24 were found to be more active than parent DHA against tested human cancer cell lines. DHA derivatives were found to be most active in human leukemia cell lines with compounds 8, 14, 15, 20 and 24 showed IC50 values less than 1 μM for 48 h whereas DHA has IC50 value of 2 μM at same time period. The most potent compounds 8 with IC50 = 0.3 μM (at par with doxorubicin (IC50 = 0.3 μM)) and 15 with IC50 = 0.4 μM, of the series, six and three times active than DHA (with IC50 = 2 μM) respectively were selected for further mechanistic work in human leukemia HL-60 cells.

Compounds DHA, 8 and 15 trigger mitochondrial potential loss in HL-60 cells and induced apoptotic bodies formation in human leukemia HL-60 cells.Figure optionsDownload as PowerPoint slide