Synthesis and cytotoxicity studies of artemisinin derivatives containing lipophilic alkyl carbon chains.

[reaction: see text] Cytotoxic artemisinin derivatives have been synthesized by a modular approach of "artemisinin + linker + lipophilic alkyl carbon chain". A strong correlation between the length of the carbon chains and the cytotoxicities against human hepatocellular carcinoma (HepG2) was revealed. Notably, compared with artemisinin (IC(50) = 97 microM), up to 200-fold more potent cytotoxicity (IC(50) = 0.46 microM) could be achieved by attachment of a C(14)H(29) carbon chain to artemisinin via an amide linker.