Discovery of novel Bis-amide analogue ST12 for the treatment of inflammatory bowel diseases (IBD) by inhibiting NLRP3 inflammasome activation.

Herein, we designed and synthesized a series of novel bis-amide small molecule anti-inflammatory agents, among them, compound ST12 showed most potent anti-inflammatory activity. ST12 effectively inhibited the production of nitric oxide (NO) (inhibition rate of 52.67 ± 0.03 % at 10 μM) and downregulated the mRNA levels of proinflammatory cytokines iNOS, IL-6, IL-1β and TNF-α in lipopolysaccharide (LPS) induced RAW264.7 cells. Furthermore, mechanism studies suggest that compound ST12 exerted anti-inflammatory effects by inhibiting the activation of the NLRP3 inflammasome. Importantly, ST12 effectively ameliorated DSS-induced colitis in vivo. Taken together, ST12 is worthy of further investigation as a small molecule anti-inflammatory agent for treatment of inflammatory bowel diseases (IBD).