Design, synthesis, and bioactivity evaluation of novel 1-(4-(benzylsulfonyl)-2-nitrophenyl) derivatives as potential anti-inflammatory agents against LPS-induced acute lung injury. (15th January 2023)

• Record Type: Journal Article
• Authors: Chen, Pan; Yu, Yiming; Su, Sijia; Du, Zhiteng; Cai, Binhao; Sun, Xiaoyu; Chattipakorn, Nipon; Samorodov, Aleksandr V.; Pavlov, Valentin N.; Tang, Qidong; Cho, Won-Jea; Liang, Guang
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 80(2023)
• Publication Date: 2023-01-15
• Subjects: Acute respiratory distress syndrome -- Acute lung injury -- Sulfur-containing compounds -- Anti-inflammatory; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2022.129097
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Designed and synthesized 36 1-(4-(benzylsulfonyl)-2-nitrophenyl) derivatives. Compound 39 showed strong activity against the release of IL-6 and TNF-α. Compound 39 inhibited the release of cytokines in lung tissue and serum. Compound 39 reduced the infiltration of neutrophils in lung tissue. Compound 39 attenuate ALI in LPS-induced mice model. Abstract: Acute lung injury (ALI) is a devastating disease with a high mortality rate of 30%–40%. There is an unmet clinical need owing to limited treatment strategies and little clinical benefit. The pathology of ALI indicates that reducing the inflammatory response could be a highly desirable strategy to treat ALI. In this study, we designed and synthesized 36 novel 1-(4-(benzylsulfonyl)-2-nitrophenyl) derivatives and evaluated their anti-inflammatory activities by measuring the release of cytokines in lipopolysaccharide (LPS)-challenged J774A.1 cells. Compounds 19, 20, and 39 potently reduced the release of IL-6 and TNF-α in J774A.1 cells. Additionally, 39 improved LPS-induced ALI in vivo and inhibited cytokine production in lung tissues. Furthermore, 39 reduced inflammatory infiltration and downregulated p-p65 levels in lung tissues. Thus, compound 39 could serve as a new lead structure for the development of anti-inflammatory drugs to treat ALI.