2. Academic Validation
  3. Design, synthesis and biological evaluation of 4-anilinoquinoline derivatives as novel potent tubulin depolymerization agents

Design, synthesis and biological evaluation of 4-anilinoquinoline derivatives as novel potent tubulin depolymerization agents

  • Eur J Med Chem. 2017 Sep 29:138:1114-1125. doi: 10.1016/j.ejmech.2017.07.040.
Yuanyuan Zhou 1,  Wei Yan 1,  Dong Cao 2,  Mingfeng Shao 1,  Dan Li 1,  Fang Wang 1,  Zhuang Yang 1,  Yong Chen 1,  Linhong He 1,  Taijin Wang 1,  Mingsheng Shen 1,  Lijuan Chen 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, 610041, China.
  • 2 Chengdu Institute of Chinese Herbal Medicine, Chengdu, 610043, China.
  • 3 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, 610041, China; School of Chemical Engineering, Sichuan University, Chengdu, China. Electronic address: chenlijuan125@163.com.
PMID: 28763646 DOI: 10.1016/j.ejmech.2017.07.040
Abstract

A series of novel 4-anilinoquinoline derivatives were synthesized and evaluated for their antiproliferative activities. Among them, 14h exhibited the most potent cytotoxic activity with IC50 values ranging from 1.5 to 3.9 nM against all tested Cancer cell lines, and showed promising efficacy in multidrug resistant Cancer cells. Flow cytometry assay, immune-fluorescence staining, microtubule dynamics assays and competition assays with EBI identified that 14h was a novel tubulin depolymerization agent by binding to the colchicine site. Importantly, in vivo efficacy evaluation of HCT116 xenograft model, 14h showed efficient antitumor activity without significant loss in body weight. All the results indicated that 14h could be a promising candidate for the treatment of Cancer.

Keywords

Antimitotic; Antiproliferative; Depolymerization; Microtubules; Quinoline.

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