Identification of Lead Compounds as Inhibitors of STAT3: Design, Synthesis and Bioactivity. Issue 10 (1st July 2015)

• Record Type: Journal Article
• Authors: Botta, Antonio; Sirignano, Esther; Popolo, Ada; Saturnino, Carmela; Terracciano, Stefania; Foglia, Antonio; Sinicropi, Maria Stefania; Longo, Pasquale; Di Micco, Simone
• Is Part Of: Molecular informatics. Volume 34:Issue 10(2015:Oct.)
• Page Start: 689
• Page End: 697
• Publication Date: 2015-07-01
• Subjects: Cheminformatics -- Periodicals; QSAR (Biochemistry) -- Periodicals; Structure-activity relationships (Biochemistry) -- Periodicals; Drugs -- Structure-activity relationships -- Periodicals; 615.19
• DOI: 10.1002/minf.201500043
• Languages: English
• ISSNs: 1868-1743

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>STAT3 belongs to the signal transducers and activators of transcription (STAT) family. It has been demonstrated that STAT3 is constitutively activated in many tumors, playing a role in carcinogenesis and tumor progression. For this reason, it has being considered a potential target for cancer therapy. In this context, we have designed, synthesized and evaluated 1, 4‐dimethyl‐carbazole derivatives, targeting the STAT3 protein. Moreover, MTT assay performed on A375 and HeLa, showed significant antiproliferative activity of some of synthesized compounds (<bold>3</bold>–<bold>5</bold>). The same compounds (<bold>3</bold>–<bold>5</bold>) considerably reduced STAT3 expression, as demonstrated by Western blot analysis. Our multidisciplinary approach shows that 1, 4‐dimethyl‐carbazoles are potential building blocks to develop more affinity ligands of STAT3.</p> </abstract>