RESUMO
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.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Isoquinolinas/isolamento & purificação , Isoquinolinas/farmacologia , Magnoliopsida/química , Naftalenos/isolamento & purificação , Naftalenos/farmacologia , África Central , Fármacos Anti-HIV/química , Humanos , Concentração Inibidora 50 , Isoquinolinas/química , Estrutura Molecular , Naftalenos/química , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Linfócitos T/efeitos dos fármacosRESUMO
From the wild-type strain Steptomyces sp. AK 671, three nitrogen-containing octaketides were isolated, bhimamycins F, H and I, besides the known azaanthraquinone utahmycin A and polyketide shunt products SEK 4, SEK 4b, mutactin, dehydromutactin and EM18. The structures were characterized by MS and NMR experiments. The hitherto unknown absolute configuration of the two enantiomers of EM18 was determined by online-CD spectroscopy and quantum-chemical CD calculations. Bhimamycins H and I show weak antibacterial activities, whereas the enzyme phosphodiesterase 4 is strongly inhibited by bhimamycins H and I, which has never been reported for nitrogen-containing octaketides. In addition, bhimamycin H inhibits the enzyme glycogen synthase kinase-3ß.
Assuntos
Antibacterianos/química , Policetídeos/química , Pirróis/química , Quinonas/química , Streptomyces/metabolismo , Antibacterianos/biossíntese , Antibacterianos/farmacologia , Fermentação , Espectroscopia de Ressonância Magnética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Estrutura Molecular , Policetídeo Sintases/metabolismo , Policetídeos/metabolismo , Policetídeos/farmacologia , Pirróis/metabolismo , Pirróis/farmacologia , Quinonas/metabolismo , Quinonas/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Staphylococcus epidermidis/efeitos dos fármacos , EstereoisomerismoRESUMO
Mbandakamines A (1) and B (2), isolated from the leaves of an as yet unidentified Congolese Ancistrocladus species, are the first dimeric naphthylisoquinoline alkaloids with an unsymmetrically coupled central biaryl axis. Their novel 6',1â³-coupling type implies a hitherto unprecedented peri-peri coupling in one of the naphthalene parts, leading to the as yet highest steric hindrance at the central axis and a total of seven elements of chirality. Mbandakamine A exhibits good antimalarial activity.