Inhibitory Effects of Nitrogenous Metabolites from a Marine-Derived Streptomyces bacillaris on Isocitrate Lyase of Candida albicans

Two nitrogenous metabolites, bacillimide (1) and bacillapyrrole (2), were isolated from the culture broth of the marine-derived actinomycete Streptomyces bacillaris. Based on the results of combined spectroscopic and chemical analyses, the structure of bacillimide (1) was determined to be a new cyclopenta[c]pyrrole-1,3-dione bearing a methylsulfide group, while the previously reported bacillapyrrole (2) was fully characterized for the first time as a pyrrole-carboxamide bearing an alkyl sulfoxide side chain. Bacillimide (1) and bacillapyrrole (2) exerted moderate (IC50 = 44.24 mu M) and weak (IC50 = 190.45 mu M) inhibitory effects on Candida albicans isocitrate lyase, respectively. Based on the growth phenotype using icl-deletion mutants and icl expression analyses, we determined that bacillimide (1) inhibits the transcriptional level of icl in C. albicans under C-2-carbon-utilizing conditions.

Automated summary

Two nitrogenous metabolites, bacillimide (1) and bacillapyrrole (2), were isolated from the culture broth of the marine-derived actinomycete Streptomyces bacillaris. Their structures were determined through spectroscopic and chemical analyses. The inhibitory effects of bacillimide (1) and bacillapyrrole (2) on Candida albicans isocitrate lyase were found to be moderate and weak, respectively.