Summary: | Four new ansamycins, named divergolides T–W (<b>1</b>–<b>4</b>), along with two known analogs were isolated from the fermentation broth of the mangrove-derived actinomycete <i>Streptomyces</i> sp. KFD18. The structures of the compounds, including the absolute configurations of their stereogenic carbons, were determined by spectroscopic data and single-crystal X-ray diffraction analysis. Compounds <b>1</b>–<b>4</b> showed cytotoxic activity against the human gastric cancer cell line SGC-7901, the human leukemic cell line K562, the HeLa cell line, and the human lung carcinoma cell line A549, with <b>1</b> being the most active while compounds <b>5</b> and <b>6</b> were inactive against all the tested cell lines. Compounds <b>1</b> and <b>3</b> showed very potent and specific cytotoxic activities (IC<sub>50</sub> 2.8 and 4.7 µM, respectively) against the SGC-7901 cells. Further, the apoptosis-inducing effect of <b>1</b> and <b>3</b> against SGC-7901 cells was demonstrated by two kinds of staining methods for the first time.
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