RESUMEN
The crude extracts of the fermentation broth from a marine sediment-derived actinomycete strain, Saccharothrix sp. 10-10, showed significant antibacterial activities against drug-resistant pathogens. A genome-mining PCR-based experiment targeting the genes encoding key enzymes involved in the biosynthesis of secondary metabolites indicated that the strain 10-10 showed the potential to produce tetracenomycin-like compounds. Further chemical investigation of the cultures of this strain led to the identification of two antibiotics, including a tetracenomycin (Tcm) analogs, Tcm X (1), and a tomaymycin derivative, oxotomaymycin (2). Their structures were identified by spectroscopic data analysis, including UV, 1D-NMR, 2D-NMR and MS spectra. Tcm X (1) showed moderate antibacterial activities against a number of drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) pathogens, with the MIC values in the range of 32-64 microg x mL(-1). In addition, 1 also displayed significant cytotoxic activities against human cancer cell lines, including HL60 (leukemia), HepG2 (liver), and MCF-7 (breast) with the IC 50 values of 5.1, 9.7 and 18.0 micromol x L(-1), respectively. Guided by the PCR-based gene sequence analysis, Tcm X (1) and oxotomaymycin (2) were identified from the genus of Saccharothrix and their 13C NMR data were correctly assigned on the basis of 2D NMR spectroscopic data analysis for the first time.
Asunto(s)
Actinomycetales/química , Antibacterianos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Actinomycetales/genética , Antibacterianos/química , Antibacterianos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Benzodiazepinonas/química , Benzodiazepinonas/aislamiento & purificación , Benzodiazepinonas/farmacología , Línea Celular Tumoral , Minería de Datos/métodos , Farmacorresistencia Bacteriana , Enterococcus faecalis/efectos de los fármacos , Fermentación , Genómica , Humanos , Concentración 50 Inhibidora , Biología Marina , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Naftacenos/química , Naftacenos/aislamiento & purificación , Naftacenos/farmacología , Filogenia , Staphylococcus epidermidis/efectos de los fármacosRESUMEN
Sophora tonkinensis is widely used as traditional Chinese medicine for treating the swelling of the gums and tongue and mouth sores due to flame stomach fire. It is mainly origin from Guangxi, Sichuan provinces of China. Alkaloids are considered as the major bioactive components. A method was established for identifying alkaloids in S. tonkinensis root by UPLC-Q-TOF-MS/MS and was applied in characterizing alkaloids in S. tonkinensis root of two different habitats. Consequently, twenty-four alkaloids including six new compounds were identified in S. tonkinensis root. Additionally, the difference of alkaloids in S. tonkinensis from Guozhou, Sichuan province was investigated. In the present study, we firstly characterize total alkaloids in S. tonkinensis root by UPLC-Q-TOF-MS/MS and firstly established the characteristic fragmentation pathway of alkaloids with hydroxy in S. tonkinensis root.