title: Bendigoles D-F, bioactive sterols from the marine sponge-derived Actinomadura sp. SBMs009.
abstract: 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 IC(50) approximated to 30 μM and was the most active inhibitor of GR-translocation, while 3 was the most effective inhibitor of NF-κB nuclear translocation with an IC(50) of 71 μM.
authors.affiliation: Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) and Saarland University, Saarbrücken, Germany.
authors.forename: Luke
authors.initials: L
authors.lastname: Simmons
authors.forename: Katrin
authors.initials: K
authors.lastname: Kaufmann
authors.forename: Ronald
authors.initials: R
authors.lastname: Garcia
authors.forename: Gertrud
authors.initials: G
authors.lastname: Schwär
authors.forename: Volker
authors.initials: V
authors.lastname: Huch
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
mesh_terms: D000192:Actinomycetales / Q000737:chemistry* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D011161:Porifera / Q000382:microbiology; D013261:Sterols / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D014162:Transfection
chemical_list: D013261:Sterols