Novel Hydrogen Sulfide Hybrid Derivatives of Keap1-Nrf2 Protein-Protein Interaction Inhibitor Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis.

ABSTRACT: Ulcerative colitis (UC) is an idiopathic inflammatory disease of unknown etiology possibly associated with intestinal inflammation and oxidative stress. Molecular hybridization by combining two drug fragments to achieve a common pharmacological goal represents a novel strategy. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway provides an effective defense mechanism for UC therapy, and hydrogen sulfide (H₂S) shows similar and relevant biological functions as well. In this work, a series of hybrid derivatives were synthesized by connecting an inhibitor of Keap1-Nrf2 protein-protein interaction with two well-established H₂S-donor moieties, respectively, via an ester linker, to find a drug candidate more effective

SUBMITTER: Zhang X 

PROVIDER: S-EPMC10215391 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature