title: Suvanine sesterterpenes from a tropical sponge Coscinoderma sp. inhibit isocitrate lyase in the glyoxylate cycle.
abstract: 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.
authors.affiliation: Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Korea. awhee84@naver.com.
authors.forename: So-Hyoung
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. wth123@snu.ac.kr.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Won
authors.affiliation: Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Korea. hqhqeori@naver.com.
authors.forename: Heegyu
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Korea. chanhong@snu.ac.kr.
authors.forename: Chan-Hong
authors.initials: CH
authors.lastname: Ahn
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. wth123@snu.ac.kr.
authors.forename: Jongheon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Korea. ohkibong@snu.ac.kr.
authors.forename: Ki-Bong
authors.initials: KB
authors.lastname: Oh
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism; D006038:Glyoxylates / Q000378:metabolism*; D007522:Isocitrate Lyase / Q000037:antagonists & inhibitors*; D010641:Phenotype; D011161:Porifera / Q000737:chemistry*; D054830:Sesterterpenes / Q000737:chemistry / Q000494:pharmacology*; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D006038:Glyoxylates; D054830:Sesterterpenes; D013729:Terpenes; C582927:suvanine; D007522:Isocitrate Lyase