LC-HRMS/MS molecular networking enabled the targeted isolation of three new neoantimycin analogs (1, 3, 5) and two known ones (2, 4) from the culture broth of Streptomyces conglobatus RJ8. After derivatization into C1-hydroxyl form compounds (6-10) respectively, the absolute structures of 1-5 were clearly determined by analyzing the hydrolyzed components from 6-10. Compounds 2 and 3 were confirmed to be a pair of epimers with different stereochemistry at C-2, and so were 4 and 5. This is the first report of the isolation and characterization of epimers of NATs. The most abundant eight compounds we obtained were subjected to a cytotoxicity assay, 1 and 6 exhibited excellent cytotoxicity with the lowest IC50 value in the picomolar range against six human carcinoma cell lines while 7 and 8 showed potent cytotoxicity against PC-9 and PC-9/GR cell lines.
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