HIV-inhibitory michellamine-type dimeric naphthylisoquinoline alkaloids from the Central African liana Ancistrocladus congolensis

• Published in: Phytochemistry (Oxford) 2016-08, Vol.128, p.71-81
• Main Authors: Bringmann, Gerhard, Steinert, Claudia, Feineis, Doris, Mudogo, Virima, Betzin, Julia, Scheller, Carsten
• Format: Article
• Language: English
• Subjects: Africa, Central; Ancistrocladaceae; Ancistrocladus congolensis; Anti-HIV activities; Anti-HIV Agents - chemistry; Anti-HIV Agents - isolation & purification; Anti-HIV Agents - pharmacology; Humans; Inhibitory Concentration 50; Isoquinolines - chemistry; Isoquinolines - isolation & purification; Isoquinolines - pharmacology; Magnoliopsida - chemistry; Michellamines; Molecular Structure; Naphthalenes - chemistry; Naphthalenes - isolation & purification; Naphthalenes - pharmacology; Naphthylisoquinoline alkaloids; Nuclear Magnetic Resonance, Biomolecular; Plant Bark - chemistry; T-Lymphocytes - drug effects
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2016.04.005

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. [Display omitted] •Michellamine-type naphthylisoquinoline dimers were isolated from Ancistrocladus congolensis.•The dimers possess three or four stereogenic centers and two chiral biaryl axes.•The dimers consist of a korupensamine A half and a modified korupensamine-type monomer.•Their stereostructures were determined by NMR, oxidative degradation, and chiroptical (CD) methods.•The michellamines A2, A3, and A4 exhibited strong anti-HIV activities.