Synthesis and in vitro biological evaluation of dihydroartemisinyl-chalcone esters

• Synthesis of a series of artemisinin-chalcone hybrids.
• Evaluation of antimalarial, cytotoxicity and antitumor activity of series.
• Several hybrids as active as DHA, but 2–3 times more active than artesunate.
• Hybrids show additive effects compared to the 1:1 molar ratio of chalcone and DHA.
• Hybrids show promising antitumor activity.

A series of dihydroartemisinyl-chalcone esters were synthesized through esterification of chalcones with dihydroartemisinin (DHA). The hybrids were screened against chloroquine (CQ) sensitive (3D7) and CQ resistant (W2) strains of intraerythrocytic Plasmodium falciparum parasites, and were all found to be active, with IC50 values ranging between 1.5 and 11 nM against both strains, with SI values over 5800. The esters featuring oxygenated aryl rings (7, 10 and 11), were found to be equipotent to DHA, but were 2–3 times more active than artesunate against the 3D7 and W2 strains of the malaria parasites. They were also screened in vitro against a panel of three cancer cell lines consisting of TK-10, UACC-62 and MCF-7. Compound 7, bearing a furan ring, displayed the most potent overall antitumor activity against all three cancer cell lines. TGA revealed that the targeted hybrids were all thermally more stable than DHA, which may be beneficial to the high temperature storage conditions that prevail in malaria endemic countries. During this study, ester 7 was identified as the best candidate for further investigation as a potential drug in search for new, safe and effective antimalarial drugs.

A series of artemisinyl-chalcone esters were synthesized and their in vitro antimalarial activity against 3D7 and W2 strains of Plasmodium falciparum determined. The in vitro cytotoxicity were determined against normal Human Fetal Lung Fibroblast (WI-38 cell line), while anticancer activities were determined against a 3-cell line panel consisting of TK-10 (renal), UACC-62 (melanoma) and MCF-7 (breast) cancer cells.Figure optionsDownload as PowerPoint slide