Discovery of novel benzene 1,3-dicarboxylic acid inhibitors of bacterial MurD and MurE ligases by structure-based virtual screening approach

作者：Perdih Andrej; Kovac Andreja; Wolber Gerhard; Blanot Didier; Gobec Stanislav; Solmajer Tom^*

来源：Bioorganic & Medicinal Chemistry Letters, 2009, 19(10): 2668-2673.

DOI：10.1016/j.bmcl.2009.03.141

• MurD and MurE enzymes
• Virtual screening
• Three-dimensional structure-based pharmacophores
• Molecular docking
• Antibacterial agents
• Drug design

The peptidoglycan biosynthetic pathway provides an array of potential targets for antibacterial drug design, attractive especially with respect to selective toxicity. Within this pathway, the members of the Mur ligase family are considered as promising emerging targets for novel antibacterial drug design. Based on the available MurD crystal structures co-crystallised with N-sulfonyl glutamic acid inhibitors, a virtual screening campaign was performed, combining three-dimensional structure-based pharmacophores and molecular docking calculations. A novel class of glutamic acid surrogates-benzene 1,3-dicarboxylic acid derivatives-were identified and compounds 14 and 16 found to possess dual MurD and MurE inhibitory activity.

• 出版日期2009-5-15