Thienochromene derivatives inhibit pSTAT1 and pSTAT5 signaling induced by cytokines

• 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. 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 IC 50 value of 5.0 µM.