Synthesis and Cytotoxic Evaluation of Artemisinin–triazole Hybrids

Abstract

Dihydroartemisinin was converted to its corresponding alkyne-functionalized esters, which were subsequently deployed as substrates for a 'click' chemistrymediated coupling with 3'-azido-3'-deoxythydimine (AZT) to furnish novel triazole-artesunate-AZT hybrid compounds. Moreover, various substituted triazole-artemisinin hybrids were synthesized based on 'click' chemistry between propargyl-substituted derivatives and artemisinin containing a 2-hydroxypropane unit. Fourteen new hybrids were thus successfully prepared and evaluated as cytotoxic agents, revealing an interesting anticancer activity of four triazole-artemisinin derivative hybrids in KB and HepG2 cancer cell lines.

Click Chemistry in Natural Product Modification

“…Structure activity relationship (SAR) studies indicated that the spacer between triazole-artiartemisinin and triazole-coumarin as well as the substituents on the coumarin were critical to the selective inhibitory activity. Artemisinin-azidothymidine hybrid b10 (IC 50 = 16.5 μ M) could exert more potent antiproliferative activity than artesunate (IC 50 = 78.5 μ M) against KB cancer cells ( Tien et al, 2016 ), indicating the azidothymidine moiety plays a key role in the increased activity. In addition, SAR studies showed that hybrids with ester triazole-linker could exert more potent antiproliferative activity than hybrids with amide triazole-linker.…”