2. Academic Validation
  3. Design, synthesis and biological evaluation of 2-phenylquinoline-4-carboxamide derivatives as a new class of tubulin polymerization inhibitors

Design, synthesis and biological evaluation of 2-phenylquinoline-4-carboxamide derivatives as a new class of tubulin polymerization inhibitors

  • Bioorg Med Chem. 2017 Nov 1;25(21):5939-5951. doi: 10.1016/j.bmc.2017.09.004.
Li Zhu 1,  Kaixiu Luo 1,  Ke Li 2,  Yi Jin 3,  Jun Lin 4
Affiliations

Affiliations

  • 1 Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
  • 2 Department of Medical Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming 650031, PR China.
  • 3 Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: jinyi@ynu.edu.cn.
  • 4 Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: linjun@ynu.edu.cn.
PMID: 28988750 DOI: 10.1016/j.bmc.2017.09.004
Abstract

A novel series of 2-phenylquinoline-4-carboxamide derivatives was synthesized, characterized and evaluated for its antiproliferative activity against five Cancer cell lines, Hela, SK-OV-3, HCT116, A549 and MDA-MB-468, and a normal human fetal lung fibroblastic cell line, MRC-5. Among them, compound 7b displayed potent cytotoxic activity in vitro against SK-OV-3 and HCT116 cell lines with IC50 values of 0.5 and 0.2μM, respectively. In general, the antiproliferative activity was correlated with the binding property of the colchicine binding site and inhibitory effect on tubulin polymerization. In addition, immunofluorescence and flow cytometry analysis revealed that selected compounds caused disruption of the mitotic spindle assembly and G2/M phase arrest of the cell cycle, which correlated with proliferation inhibitory activity. Molecular docking analysis demonstrated the interaction of 7b at the colchicine binding site of tubulin. These results indicate these compounds are promising inhibitors of tubulin polymerization for the potent treatment of Cancer.

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