title: Citrafungins A and B, two new fungal metabolite inhibitors of GGTase I with antifungal activity.
abstract: [structure: see text] Screening of natural products extracts led to the discovery of citrafungins A and B, two new fungal metabolites of the alkylcitrate family that are inhibitors of GGTase I of various pathogenic fungal species with IC(50) values of 2.5-15 microM. These compounds exhibited antifungal activities with MIC values of 0.40-55 microM. The isolation, structure elucidation, relative and absolute stereochemistry, and biological activities of citrafungins are described.
authors.affiliation: Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. sheo_singh@merck.com
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Zink
authors.forename: George A
authors.initials: GA
authors.lastname: Doss
authors.forename: Jon D
authors.initials: JD
authors.lastname: Polishook
authors.forename: Carolyn
authors.initials: C
authors.lastname: Ruby
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Register
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Kelly
authors.forename: Cynthia
authors.initials: C
authors.lastname: Bonfiglio
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Williamson
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Kelly
mesh_terms: D000475:Alkenes / Q000737:chemistry* / Q000494:pharmacology; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D007783:Lactones; C485129:citrafungin A; C485130:citrafungin B; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I