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.
Liu
Yungen
Y
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
Wong
Vincent Kam-Wai
VK
Ko
Ben Chi-Bun
BC
Wong
Man-Kin
MK
Che
Chi-Ming
CM
D000480:Alkynes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity*; D037621:Artemisinins / Q000138:chemical synthesis* / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000737:chemistry; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000480:Alkynes; D000970:Antineoplastic Agents; D037621:Artemisinins; D008055:Lipids; D012717:Sesquiterpenes; C031327:artemisinin