ABSTRACT
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.
Subject(s)
Anthraquinones/isolation & purification , Anthraquinones/pharmacology , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Anti-HIV Agents/isolation & purification , Anti-HIV Agents/pharmacology , Biological Products/isolation & purification , Biological Products/pharmacology , Anthraquinones/chemistry , Anti-Bacterial Agents/chemistry , Anti-HIV Agents/chemistry , Biological Products/chemistry , Cyclization , Drug Resistance, Viral , Microbial Sensitivity Tests , Molecular Structure , Nuclear Magnetic Resonance, BiomolecularABSTRACT
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.
Subject(s)
Bacillus/chemistry , Depsipeptides/chemistry , Depsipeptides/isolation & purification , Phosphoric Monoester Hydrolases/metabolism , British Columbia , Depsipeptides/chemical synthesis , Depsipeptides/pharmacology , Inositol Polyphosphate 5-Phosphatases , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Phosphoric Monoester Hydrolases/drug effectsABSTRACT
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.
Subject(s)
Autophagy/drug effects , Macrolides/isolation & purification , Streptomyces/chemistry , British Columbia , Macrolides/chemical synthesis , Macrolides/chemistry , Macrolides/pharmacology , Marine Biology , Models, Molecular , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , StereoisomerismABSTRACT
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).
Subject(s)
Indole Alkaloids/isolation & purification , Indole Alkaloids/pharmacology , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Phyllachorales/chemistry , British Columbia , Humans , Indole Alkaloids/chemistry , Inhibitory Concentration 50 , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, BiomolecularABSTRACT
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.