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

ORGN 611

Yungen Liu, h0292071@hkusua.hku.hk1, Vincent Kam-Wai Wong1, Ben Chi-Bun Ko1, Man-Kin Wong, mkwong@hkusua.hku.hk2, and Chi-Ming Che, cmche@hku.hk2. (1) Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China, (2) Chemistry Department & Open Lab of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, Hong Kong, China
Artemisinin (Qinghaosu) is a sesquiterpene lactone endoperoxide isolated from an ancient Chinese herb Artemisia annua. Artemisinins are highly effective against multi-drug resistant malaria caused by Plasmodium falciparum, and they have been currently used for clinical treatment of malaria. Given the remarkable success of artemisinin in the treatment of malaria, there are of growing interests to explore other therapeutic potential of artemisinin. Here we reported the synthesis and cytotoxicity studies of artemisinin derivatives containing lipophilic alkyl carbon chains. The artemisinin derivatives have been synthesized by a modular approach of “artemisinin + linker + lipophilic alkyl carbon chains”. Systematic cytotoxicity studies of the modified artemisinin derivatives revealed a strong relation between the length of the carbon chains and their cytotoxicities against human liver cancer cell line (HepG2). Notably, compared with artemisinin, up to 200-fold more potent cytotoxicity could be achieved by attachment of a 14-carbon chain to artemisinin via an amide linker.
 

Asymmetric Reactions, Heterocycles, Aromatics, Combinatorial, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 31 August 2005 Washington DC Convention Center -- Hall A, Poster

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005