N-Sulfonyl-aminobiaryls as Antitubulin Agents and Inhibitors of Signal Transducers and Activators of Transcription 3 (STAT3) Signaling
Journal
Journal of Medicinal Chemistry
Journal Volume
58
Journal Issue
16
Pages
6549-6558
Date Issued
2015
Author(s)
CHE-MING TENG
Abstract
A series of N-sulfonyl-aminobiaryl derivatives have been examined as novel antitubulin agents. Compound 21 [N-(4′-cyano-3′-fluoro-biphenyl-2-yl)-4-methoxy-benzenesulfonamide] exhibits remarkable antiproliferative activity against four cancer cell lines (pancreatic AsPC-1, lung A549, liver Hep3B, and prostate PC-3) with a mean GI50 value of 57.5 nM. Additional assays reveal that 21 inhibits not only tubulin polymerization but also the phosphorylation of STAT3 inhibition with an IC50 value of 0.2 μM. Four additional compounds (8, 10, 19, and 35) are also able to inhibit this phosphorylation. This study describes novel N-sulfonyl-aminobiaryl (biaryl-benzenesulfonamides) as potent anticancer agents targeting both STAT3 and tubulin. (Chemical Equation Presented). ? 2015 American Chemical Society.
SDGs
Other Subjects
2 (4 methoxyphenylsufonamido) (1,1' biphenyl) 4 carboxylic acid; 4 methoxy n (3',4',5' trimethoxybiphenyl 2 yl) benzenesulfonamide; 4 methoxy n [2 (pyridin 3 yl)phenyl]benzenesulfoamide; 4 methoxy n [2 (pyridin 4 yl)phenyl]benzenesulfonamide; 4 methoxy n [3' trifluoromethyl (1,1' biphenyl) 2 yl] benzenesulfonamide; 4 methoxy n [4' methoxy (1,1' biphenyl) 2 yl] benzenesulfonamide; antineoplastic agent; methyl 2' (4 methoxyphenylsufonamido) (1,1' biphenyl) 4 carboxylate; n (3' chloro 4' fluorobiphenyl 2 yl) 4 methoxybenzenesulfonamide; n (4' cyano 3' fluoro biphenyl 2 yl) 4 methoxy benzenesulfonamide; n (4' fluorobiphenyl 2 yl) 4 methoxybenzenesulfonamide; n (biphenyl 2 yl) 4 methoxybenzenesulfonamide; n [2 (furan 2 yl)phenyl] 4 methoxybenzenesulfonamide; n [3' chloro (1,1' biphenyl) 2 yl] 4 methoxybenzenesulfonamide; n [3' cyano (1,1' biphenyl) 2 yl] 4 methoxybenzenesulfonamide; n [3' fluoro (1,1' biphenyl) 2 yl] 4 methoxybenzenesulfonamide; n [3',4' difluoro (1,1' biphenyl) 2 yl] 4 methoxybenzenesulfonamide; n [3',4' dimethoxy (1,1' biphenyl) 2 yl] 4 methoxybenzenesulfonamide; n [4' chloro (1,1' biphenyl) 2 yl] 4 methoxybenzenesulfonamide; n [4' cyano (1,1' biphenyl) 2 yl] 4 methoxy n benzenesulfonamide; n [4' cyano (1,1' biphenyl) 2 yl] 4 methoxybenzenesulfonamide; n [4' cyano 3' fluoro (1,1' biphenyl) 2 yl] 4 methoxybenzenesulfonamide; n [4' hydroxy (1,1' biphenyl) 2 yl] 4 methoxybenzenesulfonamide; paclitaxel; STAT3 protein; sulfonamide; tubulin; unclassified drug; unindexed drug; vincristine; antineoplastic agent; colchicine; STAT3 protein; STAT3 protein, human; sulfonamide; tubulin modulator; antiproliferative activity; Article; controlled study; G2 phase cell cycle checkpoint; human; human cell; IC50; liver cell carcinoma; lung carcinoma; microtubule assembly; pancreas carcinoma; prostate carcinoma; protein phosphorylation; signal transduction; antagonists and inhibitors; apoptosis; binding competition; drug effects; metabolism; phosphorylation; structure activity relation; synthesis; tumor cell line; Antineoplastic Agents; Apoptosis; Binding, Competitive; Cell Line, Tumor; Colchicine; Humans; Phosphorylation; STAT3 Transcription Factor; Structure-Activity Relationship; Sulfonamides; Tubulin Modulators
Type
journal article