cytoskyrins and cytosporones produced by cytospora sp. cr200 taxonomy, fermentation and biological activitiescytoskyrins cytosporones由cytospora sp。cr200分类,发酵和生物活动.pdfVIP

Mar. Drugs 2007, 5, 71-84 Marine Drugs ISSN 1660-3397 © 2007 by MDPI /marinedrugs Full Original Paper Cytoskyrins and Cytosporones Produced by Cytospora sp. CR200: Taxonomy, Fermentation and Biological Activities Maya P. Singh 1,*, Jeffrey E. Janso 1 and Sean F. Brady 2,† 1 Natural Products Research, Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA; E-mail: jansoj@ 2 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA † Current address: Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, NY 10021; E-mail: sbrady@ * Author to whom correspondence should be addressed; E-mail: singhm@ Received: 22 June 2007 / Accepted: 8 July 2007 / Published: 19 July 2007 Abstract: In screening endophytic fungi from Costa Rica for bioactivity, fungal culture CR200, isolated from a buttonwood tree, was found to contain compounds that initiate DNA damage in a test strain of E. coli (Biochemical Induction Assay, BIA) and inhibit growth of Gram-positive bacteria, including antibiotic-resistant strains. Two new bisanthraquinones (cytoskyrins A and B) and five new related octaketides (cytosporones A-E) were isolated from fermentation broths of this fungus. Cytoskyrin A exhibited potent in-vitro antibacterial (MICs against Gram-positive bacteria, 0.03 - 0.25 μg/mL) and DNA-damaging activities (10 ng/spot), whereas cytoskyrin B was inactive in these assays. Among the cytosporones, only D and E exhibited Gra