Tetralone derivatives are MIF tautomerase inhibitors and attenuate macrophage activation and amplify the hypothermic response in endotoxemic mice.

ABSTRACT: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine playing crucial role in immunity. MIF exerts a unique tautomerase enzymatic activity that has relevance concerning its multiple functions and its small molecule inhibitors have been proven to block its pro-inflammatory effects. Here we demonstrate that some of the E-2-arylmethylene-1-tetralones and their heteroanalogues efficiently bind to MIF's active site and inhibit MIF tautomeric (enolase, ketolase activity) functions. A small set of the synthesised derivatives, namely compounds (4), (23), (24), (26) and (32), reduced inflammatory macrophage activation. Two of the selected compounds (24) and (26), however, markedly inhibited ROS and nitrite production, NF-

SUBMITTER: Garai J 

PROVIDER: S-EPMC8266241 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature