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Identification of Lead Compounds as Inhibitors of STAT3: Design, Synthesis and Bioactivity
Author(s) -
Botta Antonio,
Sirignano Esther,
Popolo Ada,
Saturnino Carmela,
Terracciano Stefania,
Foglia Antonio,
Sinicropi Maria Stefania,
Longo Pasquale,
Di Micco Simone
Publication year - 2015
Publication title -
molecular informatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.481
H-Index - 68
eISSN - 1868-1751
pISSN - 1868-1743
DOI - 10.1002/minf.201500043
Subject(s) - stat3 , hela , western blot , context (archaeology) , chemistry , cancer research , stat , carcinogenesis , computational biology , biochemistry , signal transduction , biology , cell , gene , paleontology
Abstract 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 ( 3 – 5 ). The same compounds ( 3 – 5 ) 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.