Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis

作者：Lu Xuequan; Zhang Huaning; Tonge Peter J^*; Tan Derek S

来源：Bioorganic & Medicinal Chemistry Letters, 2008, 18(22): 5963-5966.

DOI：10.1016/j.bmcl.2008.07.130

• Acyl-CoA synthetase
• Mycobacterium tuberculosis
• Staphylococcus aureus
• Mechanism-based inhibitor
• Antibiotic

Menaquinone (vitamin K-2) is an essential component of the electron transfer chain in many pathogens, including Mycobacterium tuberculosis and Staphylococcus aureus, and menaquinone biosynthesis is a potential target for antibiotic drug discovery. We report herein a series of mechanism-based inhibitors of MenE, an acyl-CoA synthetase that catalyzes adenylation and thioesterification of o-succinylbenzoic acid (OSB) during menaquinone biosynthesis. The most potent compound inhibits MenE with an IC50 value of 5.7 mu M.

• 出版日期2008-11-15