RESUMEN
Unciaphenol (2), an oxygenated analogue of the Bergman cyclization product of the enediyne uncialamycin (1), has been isolated along with 1 from cultures of the actinomycete Streptomyces uncialis. It is proposed that the C-22 OH substituent in 2 might arise from the attack of a nucleophilic oxygen species on the p-benzyne diradical intermediate IA in the Bergman cyclization of 1. 2 shows in vitro anti-HIV activity against viral strains that are resistant to clinically utilized anti-retroviral therapies.
Asunto(s)
Antraquinonas/aislamiento & purificación , Antraquinonas/farmacología , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Fármacos Anti-VIH/aislamiento & purificación , Fármacos Anti-VIH/farmacología , Productos Biológicos/aislamiento & purificación , Productos Biológicos/farmacología , Antraquinonas/química , Antibacterianos/química , Fármacos Anti-VIH/química , Productos Biológicos/química , Ciclización , Farmacorresistencia Viral , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Two new cyclic depsipeptides, turnagainolides A (1) and B (2), have been isolated from laboratory cultures of a marine isolate of Bacillus sp. The structures of 1 and 2, which are simply epimers at the site of macrolactonization, were elucidated by analysis of NMR data and chemical degradation. A total synthesis of the turnagainolides confirmed their structures. Turnagainolide B (2) showed activity in a SHIP1 activation assay.
Asunto(s)
Bacillus/química , Depsipéptidos/química , Depsipéptidos/aislamiento & purificación , Monoéster Fosfórico Hidrolasas/metabolismo , Colombia Británica , Depsipéptidos/síntesis química , Depsipéptidos/farmacología , Inositol Polifosfato 5-Fosfatasas , Biología Marina , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Monoéster Fosfórico Hidrolasas/efectos de los fármacosRESUMEN
Five new bafilomycins, F (1) to J (5), have been isolated from laboratory cultures of two Streptomyces spp. obtained from marine sediments collected in British Columbia, and their structures have been elucidated by detailed analysis of spectroscopic data and the synthesis of model compounds. The new bafilomycins F (1), G (2), H (3), and J (5) along with several co-occurring known analogues showed potent inhibition of autophagy in microscopy and biochemical assays. The thiomorpholinone fragment present in bafilomycin F (1) has not previously been found in a natural product.
Asunto(s)
Autofagia/efectos de los fármacos , Macrólidos/aislamiento & purificación , Streptomyces/química , Colombia Británica , Macrólidos/síntesis química , Macrólidos/química , Macrólidos/farmacología , Biología Marina , Modelos Moleculares , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , EstereoisomerismoRESUMEN
Laboratory cultures of the fungus Plectosphaerella cucumerina obtained from marine sediments collected in Barkley Sound, British Columbia, yielded the novel alkaloids plectosphaeroic acids A (1) to C (3). The alkaloids 1-3 are inhibitors of indoleamine 2,3-dioxygenase (IDO).
Asunto(s)
Alcaloides Indólicos/aislamiento & purificación , Alcaloides Indólicos/farmacología , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Phyllachorales/química , Colombia Británica , Humanos , Alcaloides Indólicos/química , Concentración 50 Inhibidora , Biología Marina , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Cladoniamides A-G (3- 9) have been isolated from cultures of Streptomyces uncialis, and their structures have been elucidated by a combination of spectroscopic analysis and an X-ray diffraction analysis of cladoniamide A (3). The cladoniamides have unprecedented rearranged and degraded alkaloid skeletons with putative biogenetic origins from indolocarbazole precursors. Cladoniamide G (9) is cytotoxic to MCF-7 cells in vitro at 10 microg/mL.