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Discovery of new benzensulfonamide derivatives as tripedal STAT3 inhibitors.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2018 May 10; Vol. 151, pp. 752-764. Date of Electronic Publication: 2018 Apr 04. - Publication Year :
- 2018
-
Abstract
- Persistent activated STAT3 has a striking correlation with cancer development and inhibition of STAT3 signaling pathway is a novel therapeutic way for human cancers. Among STAT family, STAT1 and STAT3 play opposite roles in tumorigenesis. However, the discovery of selective STAT3 inhibitors is still challenging to date. In this study, a series of small-molecular (MW < 500) benzensulfanilamide derivatives were designed to selectively suppress STAT3 activation for anti-cancer treatment. The most potent compound 11 inhibited both overexpressed and IL-6 induced STAT3 phosphorylation, whereas 11 displayed little effect on the phosphorylation of other STAT isoforms STAT1, STAT5, demonstrating 11 was a selective STAT3 inhibitor. Meanwhile, 11 dismissed STAT3 DNA binding activity and colony formation. In addition, 11 elevated the ROS level and induced apoptosis of cancer cells. Furthermore, 11 effectively suppressed tumor growth in an in vivo mouse-xenograft model.<br /> (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Benzene Derivatives pharmacology
Colonic Neoplasms metabolism
Colonic Neoplasms pathology
Drug Design
Female
HCT116 Cells
Humans
Mice
Mice, Nude
Models, Molecular
STAT3 Transcription Factor metabolism
Sulfonamides chemistry
Sulfonamides pharmacology
Sulfonamides therapeutic use
Antineoplastic Agents chemistry
Antineoplastic Agents therapeutic use
Apoptosis drug effects
Benzene Derivatives chemistry
Benzene Derivatives therapeutic use
Colonic Neoplasms drug therapy
STAT3 Transcription Factor antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 151
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29674294
- Full Text :
- https://doi.org/10.1016/j.ejmech.2018.03.053