title: Alkaloids from Microcos paniculata with cytotoxic and nicotinic receptor antagonistic activities.
abstract: 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 1a (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 α3β4 or α4β2 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 hα3β4 and hα4β2 receptor subtypes.
authors: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
authors: Patrick C
authors: PC
authors: Still
authors: Bitna
authors: B
authors: Yi
authors: Tatiana F
authors: TF
authors: González-Cestari
authors: Li
authors: L
authors: Pan
authors: Ryan E
authors: RE
authors: Pavlovicz
authors: Hee-Byung
authors: HB
authors: Chai
authors: Tran Ngoc
authors: TN
authors: Ninh
authors: Chenglong
authors: C
authors: Li
authors: Djaja Djendoel
authors: DD
authors: Soejarto
authors: Dennis B
authors: DB
authors: McKay
authors: A Douglas
authors: AD
authors: Kinghorn
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003110:Colonic Neoplasms / Q000188:drug therapy; D019073:HT29 Cells; D006801:Humans; D019660:Malvaceae / Q000737:chemistry*; D015394:Molecular Structure; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010880:Piperidines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014744:Vietnam
chemical_list: D000470:Alkaloids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018733:Nicotinic Antagonists; D010880:Piperidines; D011978:Receptors, Nicotinic; C580667:microgrewiapine A; C580669:microgrewiapine B; C580668:microgrewiapine C; C403531:nicotinic receptor alpha4beta2