Design, synthesis and biological evaluation of novel 2-sulfonylindoles as potential anti-inflammatory therapeutic agents for treatment of acute lung i...
Basic Information
ID: ALA4382208
Journal: Eur J Med Chem
Title: Design, synthesis and biological evaluation of novel 2-sulfonylindoles as potential anti-inflammatory therapeutic agents for treatment of acute lung injury.
Authors: Xia Q, Bao X, Sun C, Wu D, Rong X, Liu Z, Gu Y, Zhou J, Liang G.
Abstract: Acute lung injury (ALI) is primarily driven by inflammation that severely impacts lung function. Novel 2-sulfonylindoles were recently shown to exhibit anti-inflammatory activity through the inhibition of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production. Here, we synthesized 31 compounds which contained 2-sulfonylindole structure. The compounds 8a, 9g, 9h and 9k exhibited dose-dependent anti-inflammatory activity in vitro. Structural-activity relationship analysis revealed that the introduction of sulfonyl group in indole nucleus may be successful to obtain new anti-inflammatory structures and leads. The compounds 9h and 9k also decreased liposaccharide (LPS)-induced IL-6, IL-1β and vascular cell adhesion molecule-1 (VCAM-1) mRNA expression, both in vitro and in an in vivo model of ALI. Furthermore, the compounds 9h and 9k at a high dose (20 mg/kg) significantly protected against LPS-induced ALI in mice. These results show that compounds 9h and 9k could be a promising lead structure for the treatment of ALI.
CiteXplore: 30326372
DOI: 10.1016/j.ejmech.2018.10.014
Patent ID: ┄