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Cytoskyrins and Cytosporones Produced by Cytospora sp. CR200: Taxonomy, Fermentation and Biological Activities
Natural Products Research, Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
* Author to whom correspondence should be addressed.
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 Gram-positive activity, but they were inactive in the BIA. Mechanistically, cytoskyrin A specifically inhibited DNA synthesis in E. coli imp at its MIC; however, it also moderately inhibited protein synthesis at 2x its MIC. Cytoskyrin A exhibited poor cytotoxicity against tumor cell lines (IC50 > 5 μg/mL) compared to known antitumor agents. The nuclear ribosomal internal transcribed spacer region of CR200 was found to share highest similarity (94-96%) with Cytospora spp. Micro- and macroscopic morphological observations of the conidia and conidiomata, respectively, also suggested this fungus to be a Cytospora sp.
Keywords: Cytospora sp. CR200; cytoskyrins; cytosporones; antimicrobial; cytotoxic
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Singh, M.P.; Janso, J.E.; Brady, S.F. Cytoskyrins and Cytosporones Produced by Cytospora sp. CR200: Taxonomy, Fermentation and Biological Activities. Mar. Drugs 2007, 5, 71-84.
Singh MP, Janso JE, Brady SF. Cytoskyrins and Cytosporones Produced by Cytospora sp. CR200: Taxonomy, Fermentation and Biological Activities. Marine Drugs. 2007; 5(3):71-84.
Singh, Maya P.; Janso, Jeffrey E.; Brady, Sean F. 2007. "Cytoskyrins and Cytosporones Produced by Cytospora sp. CR200: Taxonomy, Fermentation and Biological Activities." Mar. Drugs 5, no. 3: 71-84.