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 !g/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 !g/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.
