A. annua to isolate, along with novel sesquiterpenes, esters of p-coumaric acid with long-chain alcohols as a mixture of six

We previously found six compounds of alkyl pcoumarates from a composite plant Artemisia annua L., and chemically synthesized these compounds (cis-isomer of C20, C22 and C24, and trans-isomer of C20, C22 and C24 of pcoumarates are compounds 1-6, respectively). This report describes the inhibitory activities of these alkyl p-coumarates against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compounds 1 and 4 weakly inhibited repair-related pol ß activity, but no compound influenced the activity of replicative pol ·. Compounds 4-6 and compounds 2 and 5 were potent inhibitors of human topos I and II, respectively. Compounds 2, 4, 5 and 6 also suppressed the growth of human colon carcinoma cell line, HCT116, with or without p53, suggesting that cell growth inhibition had the same tendency as the inhibition of topos rather than pols. Compound 5 (docosyl p-coumarate), which was the strongest inhibitor of topo II and cancer cell growth in the compounds tested, halted HCT116 p53+/+ cells in G2/M phases, and induced apoptosis, although this compound did not affect the cell cycle of HCT116 p53-/cells. These results suggest that the effect of p53-dependent cell cycle arrest may be effective for topo inhibition by compound 5. From these findings, the action mode of alkyl pcoumarates as an anti-cancer agent is discussed.