title: HIV-inhibitory michellamine-type dimeric naphthylisoquinoline alkaloids from the Central African liana Ancistrocladus congolensis.
abstract: Five michellamine-type dimeric naphthylisoquinoline alkaloids (NIQs), named michellamines A2, A3, A4, B2, and B3, have been isolated from the root bark of the Central African liana Ancistrocladus congolensisJ. Léonard (Ancistrocladaceae), along with their two known parent compounds, the michellamines A and B, which had so far only been detected in the Cameroonian species Ancistrocladus korupensis. Five monomeric representatives, viz., korupensamine D, ancistrobrevine B, hamatine, 5'-O-demethylhamatine, and 6-O-methylhamatine, already known from related Ancistrocladus species, have likewise been identified. The structure elucidation was achieved by spectroscopic analysis including HRESIMS, 1D and 2D NMR, and by chemical and chiroptical methods. The michellamines A2, A3, B3, and A4 were evaluated for their cytotoxic and anti-HIV activities at a concentration range of 0-100 μM against the HIV reference strain IIIB/LAI in A3.01 T lymphoblast cell cultures, and their effects were compared to the ones displayed by the known michellamines A and B. Inhibitory activities for HIV replication were monitored for the michellamines A2 (IC50 = 29.6 μM), A3 (IC50 = 15.2 μM), A4 (IC50 = 35.9 μM), and B (IC50 = 20.4 μM). The michellamines A and B3, by contrast, did not inhibit HIV replication. No cytotoxicity was observed. Furthermore, the chemotaxonomic significance of the previously undescribed michellamines is discussed.
authors.affiliation: Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany. Electronic address: bringman@chemie.uni-wuerzburg.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bringmann
authors.affiliation: Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Steinert
authors.affiliation: Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Feineis
authors.affiliation: Faculté des Sciences, Université de Kinshasa, B.P. 202, Kinshasa XI, The Democratic Republic of the Congo.
authors.forename: Virima
authors.initials: V
authors.lastname: Mudogo
authors.affiliation: Institute of Virology and Immunology, University of Würzburg, Versbacher Straße 7, D-97078 Würzburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Betzin
authors.affiliation: Institute of Virology and Immunology, University of Würzburg, Versbacher Straße 7, D-97078 Würzburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Scheller
mesh_terms: D000350:Africa, Central; D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019684:Magnoliopsida / Q000737:chemistry*; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D024301:Plant Bark / Q000737:chemistry; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D007546:Isoquinolines; D009281:Naphthalenes; C072235:michellamine A
keywords: Ancistrocladaceae; Ancistrocladus congolensis; Anti-HIV activities; Michellamines; Naphthylisoquinoline alkaloids