Thienochromene derivatives inhibit pSTAT1 and pSTAT5 signaling induced by cytokines

Bioorg Med Chem Lett. 2020 Sep 15;30(18):127415. doi: 10.1016/j.bmcl.2020.127415. Epub 2020 Jul 18.

Abstract

Furanocoumarins, particularly furo[3,2-c]coumarins, are found in many natural products. However, coumarins annulated to a thiophene ring have received scarce attention to date in the literature. Therefore, we synthesized 4-oxo-4H-thieno[3,2-c]chromene derivatives and tested in vitro their anti-inflammatory activity. Anti-inflammatory potential of the synthesized compounds (1, 2, 6-8, 9a-e and 10a-c) has been evaluated by measuring various pSTAT (signal transducer and activator of transcription) inhibition within the JAK (Janus-activated family kinase)/STAT signaling pathway. Ethyl 7-hydroxy-4-oxo-4H-thieno[3,2-c]chromene-2-carboxylate (7) showed best inhibition properties on pSTAT5 in GM-CSF (Granulocyte-macrophage colony-stimulating factor)-triggered PBMC assay, with IC50 value of 5.0 µM.

Keywords: Anti-inflammatory; Coumarin; Cytokine; Interleukin; JAK/STAT; Thieno[3,2-c]chromene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / pharmacology
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / pharmacology
  • Cytokines / metabolism*
  • DNA-Binding Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Janus Kinases / metabolism
  • STAT1 Transcription Factor / antagonists & inhibitors*
  • STAT5 Transcription Factor / antagonists & inhibitors*
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents
  • Benzopyrans
  • Cytokines
  • DNA-Binding Proteins
  • STAT1 Transcription Factor
  • STAT5 Transcription Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Janus Kinases