Zaragozic acids D and D2: potent inhibitors of squalene synthase and of Ras farnesyl-protein transferase

C Dufresne; K E Wilson; S B Singh; D L Zink; J D Bergstrom; D Rew; J D Polishook; M Meinz; L Huang; K C Silverman

doi:10.1021/np50101a009

Zaragozic acids D and D2: potent inhibitors of squalene synthase and of Ras farnesyl-protein transferase

J Nat Prod. 1993 Nov;56(11):1923-9. doi: 10.1021/np50101a009.

Authors

C Dufresne¹, K E Wilson, S B Singh, D L Zink, J D Bergstrom, D Rew, J D Polishook, M Meinz, L Huang, K C Silverman, et al.

Affiliation

¹ Merck Research Laboratories, Rahway, New Jersey.

PMID: 8289063
DOI: 10.1021/np50101a009

Abstract

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.

MeSH terms

Alkyl and Aryl Transferases*
Ascomycota / metabolism*
Bridged Bicyclo Compounds / isolation & purification
Bridged Bicyclo Compounds / pharmacology*
Bridged Bicyclo Compounds, Heterocyclic*
Farnesyl-Diphosphate Farnesyltransferase / antagonists & inhibitors*
Fermentation
Magnetic Resonance Spectroscopy
Transferases / antagonists & inhibitors*
Tricarboxylic Acids / isolation & purification
Tricarboxylic Acids / pharmacology*

Substances

Bridged Bicyclo Compounds
Bridged Bicyclo Compounds, Heterocyclic
Tricarboxylic Acids
zaragozic acid D
zaragozic acid D(2)
Transferases
Alkyl and Aryl Transferases
p21(ras) farnesyl-protein transferase
Farnesyl-Diphosphate Farnesyltransferase