101421-82-3Relevant articles and documents
Design, synthesis, and in vitro and biological evaluation of potent amino acid-derived thiol inhibitors of the metallo-β-lactamase IMP-1
Arjomandi, Omid Khalili,Hussein, Waleed M.,Vella, Peter,Yusof, Yusralina,Sidjabat, Hanna E.,Schenk, Gerhard,McGeary, Ross P.
, p. 318 - 327 (2016)
There are currently no clinically available inhibitors of metallo-β-lactamases (MBLs). These enzymes confer resistance to bacteria against a broad range of commonly used β-lactam antibiotics, and are produced by an increasing number of bacterial pathogens. In this study, several thiol derivatives of l-amino acids were designed and synthesized, and their inhibitory effects against the metallo-β-lactamase IMP-1 (subclass B1) were investigated. The most potent compound, derived from l-tyrosine, exhibited competitive inhibition, with a Ki of 86 nM. The ability of this compound to render MBL-expressing bacteria susceptible to imipenem was examined. Reductions in MIC values up to 5.2 - fold were observed.
Probing the activities and mechanisms of leukotriene A4 hydrolase with synthetic inhibitors
Hogg, J. Heather,Ollmann, Ian R.,Wetterholm, Anders,Andberg, Martina Blomster,Haeggstroem, Jesper,Samuelsson, Bengt,Wong, Chi-Huey
, p. 1698 - 1713 (2007/10/03)
Leukotriene (LT) A4 hydrolase catalyzes the hydrolysis of leukotriene A4 to form leukotriene B4, a potent inflammatory mediator. Recently, the synthesis and evaluation of the highly effective competitive LTA4 hydrolase inhibitor 2 (K(i) = 1.6 nM) was described. In the present study, we describe the biological activity of 2 against LTB4 biosynthesis, as well as the design, synthesis, and evaluation of a new series of inhibitors intended to probe the active site of the enzyme. On the basis of these results and of previously reported site-directed mutagenesis and inhibition studies, the mechanisms of peptide and epoxide hydrolysis catalyzed by LTA4 hydrolase are discussed.
