Design, synthesis, and bioactivity evaluation of novel 1-(4-(benzylsulfonyl)-2-nitrophenyl) derivatives as potential anti-inflammatory agents against LPS-induced acute lung injury.
Chen P, Yu Y, Su S, Du Z, Cai B, Sun X, Chattipakorn N, Samorodov AV, Pavlov VN, Tang Q, Cho WJ, Liang G.
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.