Synthesis and biological evaluation of new N-alkylcarbazole derivatives as STAT3 inhibitors: Preliminary study
| Autor: | Chiara Palladino, Antonio Botta, Carmela Saturnino, Maria Stefania Sinicropi, Mariagrazia Napoli, Marina Sala, Ettore Novellino, Hisanori Suzuki, Alessandra Carcereri de Prati |
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| Přispěvatelé: | Carmela, Saturnino, Chiara, Palladino, Mariagrazia, Napoli, Maria Stefania, Sinicropi, Antonio, Botta, Marina, Sala, Alessandra Carcereri de, Prati, Novellino, Ettore, Hisanori, Suzuki |
| Rok vydání: | 2013 |
| Předmět: |
STAT3 Transcription Factor
Pharmacology Dose-Response Relationship Drug Molecular Structure biology Kinase Chemistry Organic Chemistry Carbazoles General Medicine Cell biology Structure-Activity Relationship Biochemistry Tyrosine kinase 2 Drug Discovery Tumor Cells Cultured biology.protein Humans STAT1 STAT2 STAT3 STAT4 STAT6 |
| Zdroj: | European Journal of Medicinal Chemistry. 60:112-119 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2012.11.004 |
| Popis: | The signalling pathway of Janus tyrosine Kinases-Signal Transducers and Activators of Transcription (JAK-STAT) is activated by a number of cytokines, hormones (GH, erythropoietin and prolactin), and growth factors. JAK-STAT signalling is involved in regulation of cell proliferation, differentiation and apoptosis. These activities are due to different members of JAK-STAT family consisting of: JAK1, JAK2, JAK3, Tyk2 and STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6. Recent studies suggest a key role for STAT family proteins, in particular for STAT3, in selectively inducing and maintaining a pro-carcinogenic inflammatory microenvironment, that promote tumour cells transformation. Moreover, a striking correlation between cancer development/progression and STAT3 persistent activation exists, probably due to STAT3 promoting of the pro-oncogenic inflammatory pathways, like NF-kB, IL-6 and JAK family kinases. Recent study demonstrated that carbazoles can inhibit STAT3 mediated transcription. From these evidences, STAT3 represents a therapeutic target, so we have synthesized a new set of N-alkylcarbazole derivatives substituted in positions 2, 4 and 6, to evaluate their activity on STAT3. Some of these compounds showed an interesting activity as STAT3 selective inhibitors; in particular, compounds 9a 9b and 9c revealed to inhibit the STAT3 activation for the 50%, 90% and 95%, respectively. |
| Databáze: | OpenAIRE |
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