Oxazolomycins produced by Streptomyces glaucus and their cytotoxic activity

Six oxazolomycins (1-6) were isolated from the fermentation broth of a soil-borne bacterial strain, Streptomyces glaucus. The structures of the new compounds, oxazolomycins D-F (1-3) and glaucumycins A, B (6a/6b), were elucidated by detailed spectroscopic data analysis. Oxazolomycins 1, 2, 4, and 5 demonstrated weak or modest cytotoxic activities against four human cancer cell lines, with IC₅₀ values ranging from 10.6 ± 1.7 to 89.5 ± 6.6 μM (or >100 μM). Further study showed that 4 caused S phase cell cycle arrest in SMMC7721 cells through down-regulating the protein expression of cyclin A2, CDK2. Meanwhile, 4 induced apoptosis in SMMC7721 cells through down-regulating the protein levels of Bcl-2, up-regulating the levels of Bax, and activating the cleavage of caspase-3.