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Four epipolythiodioxopiperazine fungal metabolites ( 1 - 4 ) isolated from the sponge-derived Aspergillus quadrilineatus FJJ093 were evaluated for their capacity to inhibit isocitrate lyase (ICL) in the glyoxylate cycle of Candida albicans . The structures of these compounds were elucidated using spectroscopic techniques and comparisons with previously reported data. We found secoemestrin C ( 1 ) (an epitetrathiodioxopiperazine derivative) to be a potent ICL inhibitor, with an inhibitory concentration of 4.77 ± 0.08 μM. Phenotypic analyses of ICL -deletion mutants via growth assays with acetate as the sole carbon source demonstrated that secoemestrin C ( 1 ) inhibited C. albicans ICL. Semi-quantitative reverse-transcription polymerase chain reaction analyses indicated that secoemestrin C ( 1 ) inhibits ICL mRNA expression in C. albicans under C 2 -assimilating conditions.

Inhibitory Effects of Epipolythiodioxopiperazine Fungal Metabolites on Isocitrate Lyase in the Glyoxylate Cycle of Candida albicans