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Two new cyclized thiolopyrrolone derivatives, namely, thiolopyrrolone A (<b>1</b>) and 2,2-dioxidothiolutin (<b>2</b>), together with the kn own compound, thiolutin (<b>3</b>) were identified from a marine-derived <i>Streptomyces</i> sp. BTBU20218885, which was isolated from a mud sample collected from the coastal region of Xiamen, China. Their chemical structures were determined using spectroscopic data, including HRESIMS, 1D and 2D NMR techniques. <b>1</b> possessed a unique unsymmetrical sulfur-containing thiolopyrrolone structure. All the compounds were tested for bioactivities against <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, Bacille Calmette–Guérin (BCG), <i>Mycobacterium tuberculosis</i>, and <i>Candida albicans</i>. <b>1</b> displayed antibacterial activities against BCG, <i>M. tuberculosis</i>, and <i>S. aureus</i> with minimum inhibitory concentration (MIC) values of 10, 10, and 100 μg/mL, respectively. Thiolutin (<b>3</b>) showed antibacterial activities against <i>E. coli</i>, BCG, <i>M. tuberculosis</i>, and <i>S. aureus</i> with MIC values of 6.25, 0.3125, 0.625, and 3.125 μg/mL, respectively.