RESUMEN
Fifty-seven entomopathogenic microorganisms were screened against human pathogens and subjected to mass spectrometry molecular networking based dereplication. Isaria farinosa BSNB-1250, shown to produce potentially novel biologically active metabolites, was grown on a large scale on potato dextrose agar, and paecilosetin (1) and five new analogues (2-6) were subsequently isolated. The structures of the new compounds were elucidated using 1D and 2D NMR. The absolute configurations of compounds 1-6 were determined using Mosher ester derivatives (1, 3, 4), comparison of experimental and calculated ECD spectra (2-4 and 6), and single-crystal X-ray diffraction analysis (5). Compounds 1 and 5 exhibited strong antibacterial activity against MSSA and MRSA with MIC values of 1-2 µg/mL.
Asunto(s)
Antiinfecciosos/farmacología , Cordyceps , Pirrolidinonas/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , PaecilomycesRESUMEN
A biological evaluation of a library of extracts from entomopathogen strains showed that Pantoea sp. extract has significant antimicrobial and insecticidal activities. Three hydroxyacyl-phenylalanine derivatives were isolated from this strain. Their structures were elucidated by a comprehensive analysis of their NMR and MS spectroscopic data. The antimicrobial and insecticidal potencies of these compounds were evaluated, and compound 3 showed 67% mortality against Aedes aegypti larvae at a concentration of 100 ppm, and a minimum inhibitory concentration (MIC) of 16 µg/mL against methicillin-resistant Staphylococcus aureus. Subsequently, hydroxyacyl-phenylalanine analogues were synthesized to better understand the structure-activity relationships within this class of compounds. Bioassays highlighted the antimicrobial potential of analogues containing saturated medium-chain fatty acids (12 or 14 carbons), whereas an unsaturated long-chain fatty acid (16 carbons) imparted larvicidal activity. Finally, using a molecular networking-based approach, several close analogues of the isolated and newly synthesized lipoamino acids were discovered in the Pantoea sp. extract.
Asunto(s)
Antiinfecciosos/química , Ácidos Grasos/química , Insecticidas/química , Pantoea/química , Aedes/efectos de los fármacos , Animales , Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Ácidos Grasos/síntesis química , Ácidos Grasos/farmacología , Insecticidas/síntesis química , Insecticidas/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
Four new sesquiterpene alkaloids (1-4) with a ß-dihydroagrofuran skeleton and a new triterpenoid (5) were isolated from an ethyl acetate extract of Maytenus oblongata stems. Their structures were elucidated using 1D and 2D NMR spectroscopy as well as MS and ECD experiments. The M. oblongata stem EtOAc extract and the pure compounds isolated were tested for larvicidal activity against Aedes aegypti under laboratory conditions, and compounds 2 and 3 were found to be active.
Asunto(s)
Aedes/efectos de los fármacos , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Larva/efectos de los fármacos , Maytenus/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Alcaloides/química , Animales , Guyana Francesa , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Tallos de la Planta/química , Sesquiterpenos/química , Triterpenos/químicaRESUMEN
Endolichenic microorganisms represent a new source of bioactive natural compounds. Lichens, resulting from a symbiotic association between algae or cyanobacteria and fungi, constitute an original ecological niche for these microorganisms. Endolichenic fungi inhabiting inside the lichen thallus have been isolated and characterized. By cultivation on three different culture media, endolichenic fungi gave rise to a wide diversity of bioactive metabolites. A total of 38 extracts were screened for their anti-maturation effect on Candida albicans biofilms. The 10 most active ones, inducing at least 50% inhibition, were tested against 24 h preformed biofilms of C. albicans, using a reference strain and clinical isolates. The global molecular network was associated to bioactivity data in order to identify and priorize active natural product families. The MS-targeted isolation led to the identification of new oxygenated fatty acid in Preussia persica endowed with an interesting anti-biofilm activity against C. albicans yeasts.
RESUMEN
Natural products have proven to be an immeasurable source of bioactive compounds. The exceptional biodiversity encountered in Amazonia, alongside a rich entomofauna and frequent interactions with various herbivores is the crucible of a promising chemodiversity. This prompted us to search for novel botanical insecticides in French Guiana. As this French overseas department faces severe issues linked to insects, notably the strong incidence of vector-borne infectious diseases, we decided to focus our research on products able to control the mosquito Aedes aegypti. We tested 452 extracts obtained from 85 species originating from 36 botanical families and collected in contrasted environments against an Ae. aegypti laboratory strain susceptible to all insecticides, and a natural population resistant to both pyrethroid and organophosphate insecticides collected in Cayenne for the most active of them. Eight species (Maytenus oblongata Reissek, Celastraceae; Costus erythrothyrsus Loes., Costaceae; Humiria balsamifera Aubl., Humiriaceae; Sextonia rubra (Mez) van der Werff, Lauraceae; Piper hispidum Sw., Piperaceae; Laetia procera (Poepp.) Eichl., Salicaceae; Matayba arborescens (Aubl.) Radlk., Sapindaceae; and Cupania scrobitulata Rich., Sapindaceae) led to extracts exhibiting more than 50% larval mortality after 48 h of exposition at 100 µg/mL against the natural population and were considered active. Selectivity and phytochemistry of these extracts were therefore investigated and discussed, and some active compounds highlighted. Multivariate analysis highlighted that solvents, plant tissues, plant family and location had a significant effect on mortality while light, available resources and vegetation type did not. Through this case study we highlighted that plant defensive chemistry mechanisms are crucial while searching for novel insecticidal products.
Asunto(s)
Aedes , Insecticidas/farmacología , Extractos Vegetales/farmacología , Animales , Guyana Francesa , Larva/efectos de los fármacos , Control de MosquitosRESUMEN
The newly discovered macrolactone, mucorolactone, along with eight known compounds, was isolated from an ethyl acetate extract of the insect-borne fungus Mucor sp. All structures were elucidated using 1D and 2D NMR and MS spectroscopic experiments. Relative and absolute configurations of the original skeleton of mucorolactone was deduced from NOESY experiments, from the 13C NMR chemical shift calculation based on the DP4 probability method, and from the comparison of experimental and calculated electronic circular dichroism spectra.