Inhibitory Effects of Epipolythiodioxopiperazine Fungal Metabolites on Isocitrate Lyase in the Glyoxylate Cycle of <i>Candida albicans</i>

• Main Authors: Ji-Yeon Hwang, Beomkoo Chung, Oh-Seok Kwon, Sung Chul Park, Eunji Cho, Dong-Chan Oh, Jongheon Shin, Ki-Bong Oh
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Marine Drugs
• Subjects: epipolythiodioxopiperazines; sponge-derived fungus; <i>Aspergillus quadrilineatus</i>; <i>Candida albicans</i>; isocitrate lyase
• Online Access: https://www.mdpi.com/1660-3397/19/6/295
• ISSN: 1660-3397

Four epipolythiodioxopiperazine fungal metabolites (<b>1</b>–<b>4</b>) isolated from the sponge-derived <i>Aspergillus quadrilineatus</i> FJJ093 were evaluated for their capacity to inhibit isocitrate lyase (ICL) in the glyoxylate cycle of <i>Candida albicans</i>. The structures of these compounds were elucidated using spectroscopic techniques and comparisons with previously reported data. We found secoemestrin C (<b>1</b>) (an epitetrathiodioxopiperazine derivative) to be a potent ICL inhibitor, with an inhibitory concentration of 4.77 ± 0.08 μM. Phenotypic analyses of <i>ICL</i>-deletion mutants via growth assays with acetate as the sole carbon source demonstrated that secoemestrin C (<b>1</b>) inhibited <i>C. albicans</i> ICL. Semi-quantitative reverse-transcription polymerase chain reaction analyses indicated that secoemestrin C (<b>1</b>) inhibits <i>ICL</i> mRNA expression in <i>C. albicans</i> under C₂-assimilating conditions.