Abstract
Due to the increasing emergence of drug-resistant bacteria and tumor cell lines, novel antibiotics with antibacterial and cytotoxic activities are urgently needed. Marine actinobacteria are rich sources of novel antibiotics, and here we report the discovery of a novel alkaloid, xinghaiamine A, from a marine-derived actinomycete Streptomyces xinghaiensis NRRL B24674T. Xinghaiamine A was purified from the fermentation broth, and its structure was elucidated based on extensive spectroscopic analysis, including 1D and 2D NMR spectrum as well as mass spectrometry. Xinghaiamine A was identified to be a novel alkaloid with highly symmetric structure on the basis of sulfoxide functional group, and sulfoxide containing compound has so far never been reported in microorganisms. Biological assays revealed that xinghaiamine A exhibited broad-spectrum antibacterial activities to both Gram-negative persistent hospital pathogens (e.g. Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli) and Gram-positive ones, which include Staphylococcus aureus and Bacillus subtilis. In addition, xinghaiamine A also exhibited potent cytotoxic activity to human cancer cell lines of MCF-7 and U-937 with the IC50 of 0.6 and 0.5 µM, respectively.
Highlights
The increasing prevalence of infections caused by multi-drugresistant (MDR) bacterial pathogens has aroused worldwide concern
To evaluate the antibacterial activity of these compounds, a prebioassay was performed by collecting samples every minute and employing S. aureus as an indicator after about 20 mg crude extract was subjected to the analytical HPLC
The results indicated that the antibacterial activities of S. xinghaiensis were mainly due to this compound family, especially compound E, which we named xinghaiamine A and it exhibited antibacterial activity against S. aureus and was more purified
Summary
The increasing prevalence of infections caused by multi-drugresistant (MDR) bacterial pathogens has aroused worldwide concern. There is an urgent need to seek for new antibiotics for clinical infections caused by the MDR bacterial pathogens. Marine-derived actinomycetes are rich sources of novel secondary metabolites which harbour unique structures and have diverse biological activities such as antimicrobial, antitumor and immunosuppressive activities [6,7,8]. The obligate marine genera Salinispora and Marinispora have been characterized [9,10], and structurally unique and biologically active secondary metabolites have been isolated, such as salinosporamide A with excellent cytotoxicity from S. tropica CNB-392 and marinomycins A with strong antimicrobial and cytotoxic activities from Marinispora sp. Marine-derived streptomycetes are widely studied as novel antibiotic producers, where interesting compounds with antibacterial activities and anticancer activities were reported to be isolated [14,15]
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