Design and biological evaluation of mesalamine-NSAID hybrids targeting the NLRP3 inflammasome: a multi-target strategy for ulcerative colitis therapy.

ABSTRACT: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by epithelial damage, excessive cytokine release, and dysregulated inflammasome activation. Herein, we report the design, synthesis, and multi-targeted biological evaluation of three novel mesalamine-NSAID hybrid derivatives (D1, D3, and D4) as potential therapeutic agents for UC. Structural hybridization was employed to enhance colonic targeting, suppress NLRP3 inflammasome signaling, and reduce systemic toxicity. All compounds were characterized and screened for anti-inflammatory efficacy via qRT-PCR analysis of key inflammasome-related genes (NLRP3, IL1B, IL-18, Caspase-1) in LPS-activated macrophages. Compound D3 exhibited the most potent downregulation profile, supported by molecular docking studies showing

SUBMITTER: Yahya M 

PROVIDER: S-EPMC12808315 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature