LY2183240 regioisomers act as competitive and selective inhibitors of class C β-lactamases

Abstract

The regioisomers of the anandamide-acting drug LY2183240 exhibited specific potent and competitive inhibitory activities against class C β-lactamases. More explicitly, the 1,5- and 2,5-regioisomers inhibited AmpC from Enterobacter hormaechei (formerly Enterobacter cloacae) with inhibitor binding affinity values of 1.8 µM and 2.45 µM, respectively. Structural molecular modelling studies revealed the interaction of the regioisomers with the relevant residues of the catalytic site of cephalosporinase from E. hormaechei P99, which included Tyr150, Lys315 and Thr316.