2. Academic Validation
  3. N-Sulfonyl-aminobiaryls as Antitubulin Agents and Inhibitors of Signal Transducers and Activators of Transcription 3 (STAT3) Signaling

N-Sulfonyl-aminobiaryls as Antitubulin Agents and Inhibitors of Signal Transducers and Activators of Transcription 3 (STAT3) Signaling

  • J Med Chem. 2015 Aug 27;58(16):6549-58. doi: 10.1021/acs.jmedchem.5b00659.
Mei-Jung Lai 1,  Hsueh-Yun Lee 2,  Hsun-Yueh Chuang 2,  Li-Hsun Chang 3,  An-Chi Tsai 4,  Mei-Chuan Chen 5,  Han-Lin Huang 4,  Yi-Wen Wu 6,  Che-Ming Teng 3,  Shiow-Lin Pan 4 6,  Yi-Min Liu 2,  Samir Mehndiratta 2,  Jing-Ping Liou 2 7
Affiliations

Affiliations

  • 1 Translational Research Center, Taipei Medical University , 250 Wuxing Street, Taipei 11031, Taiwan.
  • 2 School of Pharmacy, College of Pharmacy, Taipei Medical University , 250 Wuxing Street, Taipei 11031, Taiwan.
  • 3 School of Pharmacy, College of Medicine, National Taiwan University , Taipei, Taiwan.
  • 4 The Ph.D program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University , 250 Wuxing Street, Taipei 11031, Taiwan.
  • 5 Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei Medical University , 250 Wuxing Street, Taipei 11031, Taiwan.
  • 6 Department of Pharmacology, College of Medicine, Taipei Medical University , 250 Wuxing Street, Taipei 11031, Taiwan.
  • 7 School of Pharmacy, National Defense Medical Center , Taipei, Taiwan.
PMID: 26241032 DOI: 10.1021/acs.jmedchem.5b00659
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.

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