Citrafungins A and B, two new fungal metabolite inhibitors of GGTase I with antifungal activity.
[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.
Singh
Sheo B
SB
Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. sheo_singh@merck.com
Zink
Deborah L
DL
Doss
George A
GA
Polishook
Jon D
JD
Ruby
Carolyn
C
Register
Elizabeth
E
Kelly
Theresa M
TM
Bonfiglio
Cynthia
C
Williamson
Joanne M
JM
Kelly
Rosemarie
R
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
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