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

Jun Yang; Simin Yang; Shanshan Zhou; Dongbo Lu; Liyan Ji; Zhongjun Li; Siwang Yu; Xiangbao Meng

doi:10.1016/j.ejmech.2016.07.002

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. Epub 2016 Jul 5.

Authors

Jun Yang¹, Simin Yang¹, Shanshan Zhou¹, Dongbo Lu¹, Liyan Ji¹, Zhongjun Li¹, Siwang Yu², Xiangbao Meng³

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: swang_yu@bjmu.edu.cn.
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: xbmeng@bjmu.edu.cn.

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.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / metabolism
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Benzenesulfonamides
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Screening Assays, Antitumor
Humans
Molecular Docking Simulation
Protein Multimerization
Protein Structure, Quaternary
Solubility
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / metabolism
Sulfonamides / pharmacology*
Tubulin / chemistry*
Tubulin / metabolism
Tubulin Modulators / chemical synthesis*
Tubulin Modulators / chemistry
Tubulin Modulators / metabolism
Tubulin Modulators / pharmacology*
Water / chemistry

Substances

Antineoplastic Agents
Sulfonamides
Tubulin
Tubulin Modulators
Water