Dual Inhibitor of MurD and MurE Ligases from Escherichia coli and Staphylococcus aureus

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• 作者：Tihomir Toma拧i膰 ; Roman 艩ink ; Nace Zidar ; Anja Fic ; Carlos Contreras-Martel ; Andr茅a Dessen ; Delphine Patin ; Didier Blanot ; Manica M眉ller-Premru ; Stanislav Gobec ; Anamarija Zega ; Danijel Kikelj ; Lucija Peterlin Ma拧i膷
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：August 9, 2012
• 年：2012
• 卷：3
• 期：8
• 页码：626-630
• 全文大小：253K
• 年卷期：v.3,no.8(August 9, 2012)
• ISSN：1948-5875

文摘

MurD and MurE ligases, consecutive enzymes participating in the intracellular steps of bacterial peptidoglycan biosynthesis, are important targets for antibacterial drug discovery. We have designed, synthesized, and evaluated the first d-glutamic acid-containing dual inhibitor of MurD and MurE ligases from Escherichia coli and Staphylococcus aureus (ICb>50b> values between 6.4 and 180 渭M) possessing antibacterial activity against Gram-positive S. aureus and its methicillin-resistant strain (MRSA) with minimal inhibitory concentration (MIC) values of 8 渭g/mL. The inhibitor was also found to be noncytotoxic for human HepG2 cells at concentrations below 200 渭M.<br>

Keywords:

bs.acs.org/action/doSearch?action=search&searchText=antibacterial+agent&qsSearchArea=searchText">antibacterial agent; bs.acs.org/action/doSearch?action=search&searchText=inhibitor&qsSearchArea=searchText">inhibitor; bs.acs.org/action/doSearch?action=search&searchText=Mur+ligase&qsSearchArea=searchText">Mur ligase; bs.acs.org/action/doSearch?action=search&searchText=peptidoglycan&qsSearchArea=searchText">peptidoglycan; bs.acs.org/action/doSearch?action=search&searchText=2%5C-thioxothiazolidin%5C-4%5C-one&qsSearchArea=searchText">2-thioxothiazolidin-4-one