Suvanine Sesterterpenes from a Tropical Sponge Coscinoderma sp. Inhibit Isocitrate Lyase in the Glyoxylate Cycle
- Resource Type
- article
- Authors
- So-Hyoung Lee; Tae Hyung Won; Heegyu Kim; Chan-Hong Ahn; Jongheon Shin; Ki-Bong Oh
- Source
- Marine Drugs, Vol 12, Iss 10, Pp 5148-5159 (2014)
- Subject
- Candida albicans
isocitrate lyase
Coscinoderma sp.
suvanine sesterterpenes
ICL mutants
Biology (General)
QH301-705.5
- Language
- English
- ISSN
- 1660-3397
The glyoxylate cycle is a sequence of anaplerotic reactions catalyzed by the key enzymes isocitrate lyase (ICL) and malate synthase (MLS). Mutants of Candida albicans lacking ICL are markedly less virulent in mice than the wild-type. Suvanine sesterterpenes (1−9) isolated from a tropical sponge Coscinoderma sp. were evaluated for their inhibitory activities toward recombinant ICL from C. albicans. These studies led to the identification of a potent ICL inhibitor, suvanine salt (2), which possesses a sodium counterion and displays an inhibitory concentration value (IC50) of 6.35 μM. The growth phenotype of ICL deletion mutants and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated that compound 2 inhibits the ICL mRNA expression in C. albicans under C2-carbon-utilizing conditions. The present data highlight the potential for suvanine sesterterpenes treatment of C. albicans infections via inhibition of ICL activity.