RESUMO
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.
Assuntos
Bacillus/química , Depsipeptídeos/química , Depsipeptídeos/isolamento & purificação , Monoéster Fosfórico Hidrolases/metabolismo , Colúmbia Britânica , Depsipeptídeos/síntese química , Depsipeptídeos/farmacologia , Inositol Polifosfato 5-Fosfatases , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Monoéster Fosfórico Hidrolases/efeitos dos fármacosRESUMO
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.
Assuntos
Autofagia/efeitos dos fármacos , Macrolídeos/isolamento & purificação , Streptomyces/química , Colúmbia Britânica , Macrolídeos/síntese química , Macrolídeos/química , Macrolídeos/farmacologia , Biologia Marinha , Modelos Moleculares , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , EstereoisomerismoRESUMO
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.
Assuntos
Antraquinonas/isolamento & purificação , Antraquinonas/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Antraquinonas/química , Antibacterianos/química , Fármacos Anti-HIV/química , Produtos Biológicos/química , Ciclização , Farmacorresistência Viral , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
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).
Assuntos
Alcaloides Indólicos/isolamento & purificação , Alcaloides Indólicos/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Phyllachorales/química , Colúmbia Britânica , Humanos , Alcaloides Indólicos/química , Concentração Inibidora 50 , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
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.