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Mar Drugs. 2007 Jul 19;5(3):71-84.

Cytoskyrins and cytosporones produced by Cytospora sp. CR200: taxonomy, fermentation and biological activities.

Author information

1
Natural Products Research, Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA. singhm@wyeth.com

Erratum in

  • Mar Drugs. 2009;7(2):95-6.

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 microg/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 microg/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; antimicrobial; cytoskyrins; cytosporones; cytotoxic

PMID:
18463719
PMCID:
PMC2365685

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