Alkaloids from Microcos paniculata with Cytotoxic and Nicotinic Receptor Antagonistic Activities

作者：Still Patrick C; Yi Bitna; Gonzalez Cestari Tatiana F; Pan Li; Pavlovicz Ryan E; Chai Hee Byung; Tran Ngoc Ninh; Li Chenglong; Soejarto Djaja Djendoel; McKay Dennis B; Kinghorn A Douglas^*

来源：Journal of Natural Products, 2013, 76(2): 243-249.

DOI：10.1021/np3007414

Microcos paniculata is a large shrub or small tree that grows in several countries in South and Southeast Asia. In the present study, three new piperidine alkaloids, microgrewiapines A-C (1-3), as well as three known compounds, inclusive of microcosamine A(4), 7'-(3',4'-dihydroxyphenyl)-N-[4-methoxyphenyl)ethyl]propenamide (5), and liriodenine (6), were isolated from cytotoxic fractions of the separate chloroform-soluble extracts of the stem bark, branches, and leaves of M. paniculata. Compounds 1-6 and la (microgrewiapine A 3-acetate) showed a range of cytotoxicity values against the HT-29 human colon cancer cell line. When evaluated for their effects on human alpha 3 beta 4 or alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs), several of these compounds were shown to be active as nAChR antagonists. As a result of this study, microgrewiapine A(1) was found to be a selective cytotoxic agent for colon cancer cells over normal colon cells and to exhibit nicotinic receptor antagonistic activity for both the h alpha 3 beta 4 and h alpha 4 beta 2 receptor subtypes.

• 出版日期2013-2