Bendigoles D–F, bioactive sterols from the marine sponge-derived Actinomadura sp. SBMs009

Marine derived actinomycetes have become an important source of bioactive natural products. Here we report the structure and bioactivity of the bendigoles D–F (1–3), 3-keto sterols isolated from the new marine sponge derived bacterium, Actinomadura sp. SBMs009. The isolation of these compounds was guided by a novel high-content screen for NF-κB and glucocorticoid receptor (GR) activity, and cytotoxicity assays. The structures of 1–3 were determined by detailed analysis of NMR, MS, and single crystal X-ray diffraction data. Interestingly, 1 displayed cytotoxicity against the L929 (mouse fibroblast) cell line with an IC50 approximated to 30μM and was the most active inhibitor of GR-translocation, while 3 was the most effective inhibitor of NF-κB nuclear translocation with an IC50 of 71μM.