-
Tytuł:
-
Discovery of N-substituted sulfamoylbenzamide derivatives as novel inhibitors of STAT3 signaling pathway based on Niclosamide.
-
Autorzy:
-
Wang X; Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Wu K; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Fang L; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Yang X; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Zheng N; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Du Z; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Lu Y; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Xie Z; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Liu Z; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Zuo Z; Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. Electronic address: .
Ye F; Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. Electronic address: .
-
Źródło:
-
European journal of medicinal chemistry [Eur J Med Chem] 2021 Jun 05; Vol. 218, pp. 113362. Date of Electronic Publication: 2021 Mar 17.
-
Typ publikacji:
-
Journal Article
-
Język:
-
English
-
Imprint Name(s):
-
Publication: Paris : Editions Scientifiques Elsevier
Original Publication: Paris, S.E.C.T. [etc.]
-
MeSH Terms:
-
Drug Discovery*
Benzamides/*pharmacology
Niclosamide/*pharmacology
STAT3 Transcription Factor/*antagonists & inhibitors
Benzamides/chemical synthesis ; Benzamides/chemistry ; Dose-Response Relationship, Drug ; Humans ; Molecular Structure ; Niclosamide/chemical synthesis ; Niclosamide/chemistry ; STAT3 Transcription Factor/metabolism ; Signal Transduction/drug effects ; Structure-Activity Relationship
-
Contributed Indexing:
-
Keywords: Anti-tumor activity; N-substituted sulfamoylbenzamide STAT3 inhibitors; Niclosamide
-
Substance Nomenclature:
-
0 (Benzamides)
0 (STAT3 Transcription Factor)
0 (STAT3 protein, human)
6X80438640 (benzamide)
8KK8CQ2K8G (Niclosamide)
-
Entry Date(s):
-
Date Created: 20210328 Date Completed: 20210806 Latest Revision: 20210806
-
Update Code:
-
20240105
-
DOI:
-
10.1016/j.ejmech.2021.113362
-
PMID:
-
33774344
-
Signal transducer and activator of transcription 3 (STAT3) has been confirmed as an attractive therapeutic target for cancer therapy. Herein, we designed and synthesized a series of N-substituted Sulfamoylbenzamide STAT3 inhibitors based on small-molecule STAT3 inhibitor Niclosamide. Compound B12, the best active compound of this series, was identified as an inhibitor of IL-6/STAT3 signaling with an IC 50 of 0.61-1.11 μM in MDA-MB-231, HCT-116 and SW480 tumor cell lines with STAT3 overexpression, by inhibiting the phosphorylation of STAT3 of Tyr705 residue and the expression of STAT3 downstream genes, inducing apoptosis and inhibiting the migration of cancer cells. Furthermore, in vivo study revealed that compound B12 suppressed the MDA-MB-231 xenograft tumor growth in nude mice at the dose of 30 mg/kg (i.g.), which has better antitumor activity than the positive control Niclosamide. More importantly, B12 is an orally bioavailable anticancer agent as a promising candidate for further development.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
