The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity

M J Dawson; J E Farthing; P S Marshall; R F Middleton; M J O'Neill; A Shuttleworth; C Stylli; R M Tait; P M Taylor; H G Wildman

doi:10.7164/antibiotics.45.639

The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity

J Antibiot (Tokyo). 1992 May;45(5):639-47. doi: 10.7164/antibiotics.45.639.

Authors

M J Dawson¹, J E Farthing, P S Marshall, R F Middleton, M J O'Neill, A Shuttleworth, C Stylli, R M Tait, P M Taylor, H G Wildman, et al.

Affiliation

¹ Department of Natural Products Discovery, Glaxo Group Research Ltd., Greenford, Middlesex, UK.

PMID: 1624366
DOI: 10.7164/antibiotics.45.639

Abstract

During the screening of fungi for inhibitors of squalene synthase, Phoma sp. C2932 was found to produce three structurally related novel inhibitors. These compounds, designated the squalestatins, exhibited potent activity against both mammalian (rat liver) and fungal (Candida albicans) squalene synthase. Furthermore, they also had broad spectrum in vitro antifungal activity.

MeSH terms

Animals
Antifungal Agents / chemistry
Antifungal Agents / isolation & purification
Antifungal Agents / pharmacology*
Bridged Bicyclo Compounds / chemistry
Bridged Bicyclo Compounds / isolation & purification
Bridged Bicyclo Compounds / pharmacology*
Bridged Bicyclo Compounds, Heterocyclic*
Farnesyl-Diphosphate Farnesyltransferase / antagonists & inhibitors*
Fungi / drug effects
Microbial Sensitivity Tests
Rats
Tricarboxylic Acids / chemistry
Tricarboxylic Acids / isolation & purification
Tricarboxylic Acids / pharmacology*

Substances

Antifungal Agents
Bridged Bicyclo Compounds
Bridged Bicyclo Compounds, Heterocyclic
Tricarboxylic Acids
squalestatin 1
Farnesyl-Diphosphate Farnesyltransferase