Phosphonosulfonates are potent, selective inhibitors of dehydrosqualene synthase and staphyloxanthin biosynthesis in Staphylococcus aureus

…, F Yin, M Hensler, CA Rodrigues Poveda…

Index: Song, Yongcheng; Lin, Fu-Yang; Yin, Fenglin; Hensler, Mary; Poveda, Carlos A. Rodrigues; Mukkamala, Dushyant; Cao, Rong; Wang, Hong; Morita, Craig T.; Pacanowska, Dolores Gonzalez; Nizet, Victor; Oldfield, Eric Journal of Medicinal Chemistry, 2009 , vol. 52, # 4 p. 976 - 988

Full Text: HTML

Citation Number: 42

Abstract

Staphylococcus aureus produces a golden carotenoid virulence factor called staphyloxanthin (STX), and we report here the inhibition of the enzyme, dehydrosqualene synthase (CrtM), responsible for the first committed step in STX biosynthesis. The most active compounds are halogen-substituted phosphonosulfonates, with K i values as low as 5 nM against the enzyme and IC50 values for STX inhibition in S. aureus as low as 11 nM. ...