Discovery of Novel 5-Benzylidenerhodanine and 5-Benzylidenethiazolidine-2,4-dione Inhibitors of MurD Ligase

作者：Zidar Nace; Tomasic Tihomir; Sink Roman; Rupnik Veronika; Kovac Andreja; Turk Samo; Patin Delphine; Blanot Didier; Martel Carlos Contreras; Dessen Andrea; Premru Manica Mueller; Zega Anamarija; Gobec Stanislav; Masic Lucija Peterlin^*; Kikelj Danijel

来源：Journal of Medicinal Chemistry, 2010, 53(18): 6584-6594.

DOI：10.1021/jm100285g

We have designed, synthesized, and evaluated 5-benzylidenerhodanine- and 5-benzylidenethiazolidine-2,4-dione-based compounds as inhibitors of bacterial enzyme MurD with E. coli IC(50) in the range 45-206 mu M. The high-resolution crystal structure of MurD in complex with (R,Z)-2-(3-[{4-([2,4-dioxothiazolidin-5-ylidene]methyl)phenylamino}methyl)benzamido)pentanedioic acid [(R)-32] revealed details of the binding mode of the inhibitor within the active site and provides a good foundation for structure-based design of a novel generation of MurD inhibitors.

• 出版日期2010-9-23
• 单位中国地震局