Synthesis of novel 5-amido-2-carboxypyrazines as inhibitors of the type three secretion system of Salmonella enterica serovar Typhimurium.

A series of novel 5-amido-2-carboxypyrazine derivatives were designed, synthesized and evaluated for the inhibitory activities against the T3SS of Salmonella enterica serovar Typhimurium. Preliminary results displayed that the compounds 2f, 2g, 2h and 2i showed potent inhibitory activities against T3SS. Compound 2h was identified as the most potent T3SS inhibitor and the SPI-1 effector secretion was strongly inhibited by 2h in a dose-dependent manner. The effects of compound 2h on the SPI-1 genes transcription might be via impacting the SicA/InvF regulatory pathway.