RESUMEN
The bacillamides are a class of indole alkaloids produced by the Bacillus genus that possess significant antialgal activity. Incorporation of fluorine into the bacillamides was carried out using a precursor-directed biosynthesis approach, with 4-, 5-, and 6-fluorotryptophan added to growing cultures of Bacillus atrophaeus IMG-11. This yielded the corresponding fluorinated analogues of bacillamides A and C, in addition to new derivatives of the related metabolite N-acetyltryptamine, thus demonstrating a degree of plasticity in the bacillamide biosynthetic pathway. The bacillamide derivatives were tested for activity against bloom-forming algae, which revealed that fluorination could improve the antialgal activity of these compounds in a site-specific manner, with fluorination at the 6-position consistently resulting in improved activity.
Asunto(s)
Bacillus , Tiazoles , Triptaminas , Bacillus/metabolismo , Triptaminas/química , Tiazoles/química , HalogenaciónRESUMEN
The emergence of drug resistant microbes over recent decades represents one of the greatest threats to human health; the resilience of many of these organisms can be attributed to their ability to produce biofilms. Natural products have played a crucial role in drug discovery, with microbial natural products in particular proving a rich and diverse source of antimicrobial agents. During antimicrobial activity screening, the strain Pseudomonas mosselii P33 was found to inhibit the growth of multiple pathogens. Following chemical investigation of this strain, pseudopyronines A-C were isolated as the main active principles, with all three pseudopyronines showing outstanding activity against Staphylococcus aureus. The analogue pseudopyronine C, which has not been well-characterized previously, displayed sub-micromolar activity against S. aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa. Moreover, the inhibitory abilities of the pseudopyronines against the biofilms of S. aureus were further studied. The results indicated all three pseudopyronines could directly reduce the growth of biofilm in both adhesion stage and maturation stage, displaying significant activity at micromolar concentrations.
RESUMEN
Chemical investigation of a Pseudomonas aeruginosa strain isolated from Hebei, China, led to the isolation of a suite of quinolones, quinolone-N-oxides, and phenazines, the structures of which were elucidated by detailed spectroscopic analysis. Most notable among the secondary metabolites isolated was an unprecedented 4-quinolone containing an S-methyl group in the side chain and a new derivative including a phenyl ring in the side chain, which expand significantly the variety of structural motifs found in the quinolones and raise interesting questions about their biosynthesis.
Asunto(s)
Pseudomonas aeruginosa/química , Quinolonas/química , Cromatografía Líquida de Alta Presión/métodos , Fermentación , Análisis Espectral/métodosRESUMEN
A chemical investigation of a Chinese Pseudomonas aurantiaca strain has yielded a new benzoquinone (4) and furanone (5), in addition to the known dialkylresorcinols 1 and 2. Extensive decomposition studies on the major metabolite 1 produced an additional furanone derivative (6), a hydroxyquinone (7), and two unusual resorcinol and hydroxyquinone dimers (8 and 9). Structures were elucidated by nuclear magnetic resonance spectroscopy in combination with tandem mass spectrometry analysis. These studies illustrate the potential of artifacts as a source of additional chemical diversity. Compounds 1 and 2 showed moderate antibacterial activity against a panel of Gram-positive pathogens, while the antibacterial activities of the artifacts (4-9) were reduced.
Asunto(s)
Antibacterianos/aislamiento & purificación , Pseudomonas/química , Resorcinoles/aislamiento & purificación , Antibacterianos/química , Pueblo Asiatico , Humanos , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
This review outlines the research that was carried out regarding the isolation of bioactive compounds from marine-derived bacteria and fungi by China-based research groups from 2009-2018, with 897 publications being surveyed. Endophytic organisms featured heavily, with endophytes from mangroves, marine invertebrates, and marine algae making up more than 60% of the microbial strains investigated. There was also a strong focus on fungi as a source of active compounds, with 80% of publications focusing on this area. The rapid increase in the number of publications in the field is perhaps most notable, which have increased more than sevenfold over the past decade, and suggests that China-based researchers will play a major role in marine microbial natural products drug discovery in years to come.
Asunto(s)
Organismos Acuáticos/química , Bacterias/química , Descubrimiento de Drogas , Hongos/química , Alcaloides/química , Alcaloides/aislamiento & purificación , China , Péptidos/química , Péptidos/aislamiento & purificación , Policétidos/química , Policétidos/aislamiento & purificación , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
BACKGROUND: The current investigation sought to explore the nature of the secondary metabolites in the algae, Laurencia pacifica. RESULTS: This report details the first isolation of the sesquiterpenes isoaplysin (1), isolaurenisol (2), debromoisolaurinterol (3), debromoaplysinol (4), laur-11-en-10-ol (5), 10α-hydroxyldebromoepiaplysin (6), and the previously unknown 10-bromo-3,7,11,11-tetramethylspiro[5.5]undeca-1,7-dien-3-ol (7) from the algae, Laurencia pacifica. Isoaplysin (1) and debromoaplysinol (4) showed promising levels of growth inhibition against a panel cancer-derived cell lines of colon (HT29), glioblastoma (U87, SJ-G2), breast (MCF-7), ovarian (A2780), lung (H460), skin (A431), prostate (Du145), neuroblastoma (BE2-C), pancreas (MIA), murine glioblastoma (SMA) origin with average GI50 values of 23 and 14 µM. CONCLUSIONS: Isoaplysin (1) and debromoaplysinol (4) were up to fourfold more potent in cancer-derived cell populations than in non-tumor-derived normal cells (MCF10A). These analogues are promising candidates for anticancer drug development. Graphical Abstract á .