Zaragozic acids D and D2: potent inhibitors of squalene synthase and of Ras farnesyl-protein transferase.
Two new zaragozic acids, D and D2, have been isolated from the keratinophilic fungus Amauroascus niger. Zaragozic acids D [4] and D2 [5] are related to the previously described zaragozic acids A [1], B [2], and C [3] and are potent inhibitors of squalene synthase. Furthermore, all the zaragozic acids (A, B, C, D, and D2) are also active against farnesyl transferase. Zaragozic acids D and D2 inhibit farnesyl transferase with IC50 values of 100 nM, while zaragozic acids A and B are less potent.
Dufresne
C
C
Merck Research Laboratories, Rahway, New Jersey.
Wilson
K E
KE
Singh
S B
SB
Zink
D L
DL
Bergstrom
J D
JD
Rew
D
D
Polishook
J D
JD
Meinz
M
M
Huang
L
L
Silverman
K C
KC
D019883:Alkyl and Aryl Transferases; D001203:Ascomycota / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D005285:Fermentation; D009682:Magnetic Resonance Spectroscopy; D014166:Transferases / Q000037:antagonists & inhibitors*; D014233:Tricarboxylic Acids / Q000302:isolation & purification / Q000494:pharmacology*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D014233:Tricarboxylic Acids; C085395:zaragozic acid D; C085396:zaragozic acid D(2); D014166:Transferases; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D013186:Farnesyl-Diphosphate Farnesyltransferase