Thienochromene derivatives inhibit pSTAT1 and pSTAT5 signaling induced by cytokines. Issue 18 (15th September 2020)

• Record Type: Journal Article
• Authors: Wittine, Karlo; Antolović, Roberto; Jelić, Dubravko; Bracanović, Sara; Cetina, Mario; Andjelkovic, Uroš; Wittine, Ozren; Kraljević Pavelić, Sandra; Vinter, Adrijana
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 18(2020)
• Publication Date: 2020-09-15
• Subjects: DMSO dimethyl sulfoxide -- ELISA enzyme-linked immunosorbent assay -- FBS fetal bovine serum -- GM-CSF granulocyte-macrophage colony-stimulating factor -- IFNα inerferon alpha -- IL-2 interleukine-2 -- JAK Janus kinase -- PathScan Intracellular Signaling Array Kit -- PBMC peripheral blood mononuclear cell -- PBS phosphate buffered saline -- STAT signal transducer and activator of transcription; XRDYDKQPEUTKOZ-UHFFFAOYSA-N -- JXWPVKTZTZYXNN-UHFFFAOYSA-N -- WSGXYNCVIUSDGM-UHFFFAOYSA-N -- UQXVYUODSBIAGJ-UHFFFAOYSA-N -- ZLRYSLHVRPSJMO-UHFFFAOYSA-N -- YJDFITHISLLEBT-UHFFFAOYSA-N -- XUEJBMPAUSXSBT-UHFFFAOYSA-N -- MKGZCNQVWIDXIT-UHFFFAOYSA-N -- WRCVZCJJBWFEKM-UHFFFAOYSA-N -- HAJLTRREQIWHTN-UHFFFAOYSA-N -- STMSQPCRMHMFIW-UHFFFAOYSA-N; Thieno[3, 2-c]chromene -- Coumarin -- Anti-inflammatory -- Interleukin -- Cytokine -- JAK/STAT; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127415
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Thienochromene derivatives show anti-inflammatory potential. Hydroxyl group of coumarin scaffold is important for activity. Ethyl 7-hydroxy-4-oxo-4 H -thieno[3, 2- c ]chromene-2-carboxylate inhibited pSTAT5 production in PBMCs triggered with IL-2 and GM-CSF, as well as pSTAT1 production in PBMCs triggered with IFNα in a micromolar range. 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-4 H -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-4 H -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.