Invited Speaker

Novel synthetic cis-terpenones from natural bioactive terpene quinone methides
QIBING ZHOU, DC Ghislaine Mayer, Jennifer K Stewart

Diterpene and triterpene quinone methides are a category of closely related natural products that are isolated from the roots of plants such as Salvia pachyphylla and the thunder of god vine. Although these compounds exhibit potent antitumor and anti-inflammatory activity, the high cytotoxicity prevents further clinic applications. We found that the generation of reactive oxygen species in the oxidation process is a major cause of toxicity. Thus, the structural modification of the quinone methide chemophore in our laboratory produced an interesting synthetic analog, oxidized 2-hydroxy-cis-terpenone (OHCT). In contrast to the high toxicity of the natural quinone methides, OHCT exhibited low toxicity in cell and mice studies. The biological activity of OHCT revealed to be both chemopreventive and anti-malarial. OHCT significantly blocks the carcinogenic conversion of aflatoxin B1 in liver HepG2 cells as well as polyaromatic hydrocarbon induced P450 1A/1B activity, which are regarded as one of causes of hepatocellular carcinoma. OHCT at nanomolar concentrations is effective against all intraerythrocytic stages of Plasmodium falciparum and resistant strains. Moreover, OHCT exhibited potent activity against gametocytes, the form that is transmitted by mosquitoes and essential for the spread of malaria.