Synthesis, anti-cancer evaluation of benzenesulfonamide derivatives as potent tubulin-targeting agents

  • Eur J Med Chem. 2016 Oct 21:122:488-496. doi: 10.1016/j.ejmech.2016.07.002.
Jun Yang  1 ,  Simin Yang  1 ,  Shanshan Zhou  1 ,  Dongbo Lu  1 ,  Liyan Ji  1 ,  Zhongjun Li  1 ,  Siwang Yu  2 ,  Xiangbao Meng  3
Affiliations
  • 1. The State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
  • 2. The State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: [email protected].
  • 3. The State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: [email protected].
PMID: 27423028 DOI: 10.1016/j.ejmech.2016.07.002
Abstract

A series of benzenesulfonamide derivatives were synthesized and evaluated for their anti-proliferative activity and interaction with tubulin. These new derivatives showed significant activities against cellular proliferative and tubulin polymerization. Compound BA-3b proved to be the most potent compound with IC50 value ranging from 0.007 to 0.036 μM against seven Cancer cell lines, and three drug-resistant Cancer cell lines, which indicated a promising anti-cancer agent. The target tubulin was also verified by dynamic tubulin polymerization assay and tubulin intensity assay.

Keywords
Benzodiazepine; Benzothiazepine; Benzoxazepine; Sulfonamides; Tubulin-targeting agents.