Thienochromene derivatives inhibit pSTAT1 and pSTAT5 signaling induced by cytokines
| Autor: | Mario Cetina, Dubravko Jelić, Adrijana Vinter, Sara Bracanović, Roberto Antolović, Uroš Andjelković, Ozren Wittine, Karlo Wittine, Sandra Kraljević Pavelić |
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| Rok vydání: | 2020 |
| Předmět: |
Thieno[3
2-c]chromene Coumarin Anti-inflammatory Interleukin Cytokine JAK/STAT medicine.drug_class medicine.medical_treatment Clinical Biochemistry Anti-Inflammatory Agents Pharmaceutical Science 010402 general chemistry 01 natural sciences Biochemistry Structure-Activity Relationship chemistry.chemical_compound Thieno[3 2-c]chromene Drug Discovery STAT5 Transcription Factor medicine Humans Benzopyrans Amino Acid Sequence Molecular Biology IC50 Janus Kinases 010405 organic chemistry Kinase Chemistry Organic Chemistry Granulocyte-Macrophage Colony-Stimulating Factor JAK-STAT signaling pathway In vitro 0104 chemical sciences 3. Good health DNA-Binding Proteins STAT1 Transcription Factor STAT protein Cytokines Molecular Medicine Signal Transduction |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2020.127415 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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