A novel indazole derivative, compound Cyy-272, attenuates LPS-induced acute lung injury by inhibiting JNK phosphorylation

Toxicol Appl Pharmacol. 2021 Oct 1:428:115648. doi: 10.1016/j.taap.2021.115648. Epub 2021 Jul 17.

Abstract

Acute lung injury (ALI) is a diffuse lung dysfunction disease characterized by high prevalence and high mortality. Thus far, no effective pharmacological treatment has been made for ALI in clinics. Inflammation is critical to the development of ALI. Therefore, anti-inflammation may be a potential therapy strategy for ALI. Indazole-containing derivatives, representing one of the most important heterocycles in drug molecules, are endowed with a broad range of biological properties, such as anti-cancer and anti-inflammation. In the current study, we investigated the biological effects of Cyy-272, a newly synthesized indazole compound, on LPS-induced ALI both in vivo and in vitro. Results show that Cyy-272 can inhibit the release of inflammatory cytokines in LPS-stimulated macrophage and alleviate LPS induced ALI. Further experiment revealed that Cyy-272 exhibit anti-inflammation activity by inhibiting JNK phosphorylation. Overall, our studies show that an indazole derivative, Cyy-272, is effective in suppressing LPS-induced JNK activation and inflammatory signaling.

Keywords: ALI; Indazole compound; Inflammatory; JNK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced*
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / prevention & control*
  • Animals
  • Dose-Response Relationship, Drug
  • Indazoles / chemistry
  • Indazoles / pharmacology
  • Indazoles / therapeutic use*
  • Lipopolysaccharides / toxicity*
  • MAP Kinase Kinase 4 / antagonists & inhibitors*
  • MAP Kinase Kinase 4 / chemistry
  • MAP Kinase Kinase 4 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Phosphorylation / drug effects
  • Phosphorylation / physiology
  • Protein Structure, Tertiary
  • RAW 264.7 Cells

Substances

  • Indazoles
  • Lipopolysaccharides
  • MAP Kinase Kinase 4