Discovery of 6-Acylamino/Sulfonamido Benzoxazolone with IL-6 Inhibitory Activity as Promising Therapeutic Agents for Ulcerative Colitis.

Ulcerative colitis has been widely concerned for its persistent upward trend and sustained overproduction of pro-inflammatory cytokines such as IL-6 remains a crucial factor in UC development. Therefore, identification of new effective drugs to block inflammatory responses is an urgent and viable strategy for UC. In our research, twenty-three 6-acylamino/sulfonamido benzoxazolone derivatives were synthesized, characterized, and evaluated for anti-inflammatory activity against NO and IL-6 in LPS-induced RAW264.7 cells. The results demonstrated that most of the target compounds were capable of reducing the overexpression of NO and IL-6 to a certain degree. For the most active compounds 3i, 3j and 3l, the inhibitory activities were superior or equivalent to those of the positive drug celecoxib with a dose-dependent relationship. Furthermore, animal experiments revealed that compounds 3i, 3j and 3l exhibited definitive effect on DSS induced ulcerative colitis by mitigating weight loss and DAI score while decreasing levels of pro-inflammatory cytokines such as IL-6 and IFN-γ, simultaneously increasing production of anti-inflammatory cytokines IL-10. Additionally, compounds 3i, 3j and 3l could inhibit oxidative stress to alleviate ulcerative colitis by decreasing MDA and MPO levels. These finding demonstrated that compounds 3i, 3j and 3l hold significant potential as novel therapeutic agents for ulcerative colitis.