Design, synthesis, and bioactivity evaluation of novel amide/sulfonamide derivatives as potential anti-inflammatory agents against acute lung injury and ulcerative colitis

The uneven regulation of inflammation is related to various diseases, making anti-inflammation a potential option for the development of novel therapies. In this study, we designed and synthesized a total of fifty-eight novel amide/sulfonamide derivatives based on our previously reported anti-inflammatory compounds. The anti-inflammatory activities of these compounds were evaluated upon LPS-stimulated J774A.1 cells. Compounds 11a, 11b, 11c, and 11d potently reduced the release of IL-6 and TNF-alpha, and decreased the mRNA level of cytokines in J774A.1 cells. The most active compound 11d with IC50 value of 0.61 mu M for IL-6 inhibition, and 4.34 mu M for TNF-alpha inhibition restored I.B a and inhibited the translocation of phosphorylated p65 into the nucleus. In vivo evaluation indicated that 11d improved LPS-induced ALI and alleviated DSS-induced ulcerative colitis in mice. In conclusion, these results suggested compound 11d can be a new lead structure for the development of anti-inflammatory drugs against ALI and ulcerative colitis.

Automated summary

The uneven regulation of inflammation is related to various diseases, and anti-inflammation shows potential for the development of novel therapies. In this study, a series of novel amide/sulfonamide derivatives were designed and synthesized. Compound 11d exhibited strong anti-inflammatory activities through the inhibition of IL-6 and TNF-alpha and the modulation of cellular signaling pathways. In vivo studies demonstrated that compound 11d improved LPS-induced ALI and alleviated DSS-induced ulcerative colitis in mice.