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Eur J Med Chem. 2015 May 5;95:127-35. doi: 10.1016/j.ejmech.2015.03.035. Epub 2015 Mar 18.

Design, synthesis and biological evaluation of colchicine derivatives as novel tubulin and histone deacetylase dual inhibitors.

Author information

1
Institute of Drug Discovery and Development, East China Normal University, Shanghai 200062, PR China.
2
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, PR China.
3
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
4
National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
5
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, PR China. Electronic address: yffang@sat.ecnu.edu.cn.
6
Institute of Drug Discovery and Development, East China Normal University, Shanghai 200062, PR China. Electronic address: wlu@chem.ecnu.edu.cn.

Abstract

A new class of colchicine derivatives were designed and synthesized as tubulin-HDAC dual inhibitors. Biological evaluations of these hybrids included the inhibitory activity of HDAC, tubulin polymerization analysis, in vitro cell cycle analysis in HCT-116 cells and cytotoxicity against different cancer cell lines. Hybrid 6d behaved as potent HDAC-tubulin dual inhibitor and showed comparable cytotoxicity with colchicine. Compound 11a exhibited powerful tubulin inhibitory activity, moderate anti-HDAC activity and the most potent cytotoxicity (IC50 = 2-105 nM).

KEYWORDS:

Colchicine; Dual inhibitor; HDAC; Hybrid; Tubulin

PMID:
25805446
DOI:
10.1016/j.ejmech.2015.03.035
[Indexed for MEDLINE]

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