title: Design, synthesis and biological evaluation of colchicine derivatives as novel tubulin and histone deacetylase dual inhibitors.
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).
authors: Institute of Drug Discovery and Development, East China Normal University, Shanghai 200062, PR China.
authors: Xuan
authors: X
authors: Zhang
authors: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, PR China.
authors: Yannan
authors: Y
authors: Kong
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors: Jie
authors: J
authors: Zhang
authors: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors: Mingbo
authors: M
authors: Su
authors: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors: Yubo
authors: Y
authors: Zhou
authors: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors: Yi
authors: Y
authors: Zang
authors: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors: Jia
authors: J
authors: Li
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors: Yi
authors: Y
authors: Chen
authors: 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.
authors: Yanfen
authors: Y
authors: Fang
authors: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, PR China.
authors: Xiongwen
authors: X
authors: Zhang
authors: Institute of Drug Discovery and Development, East China Normal University, Shanghai 200062, PR China. Electronic address: wlu@chem.ecnu.edu.cn.
authors: Wei
authors: W
authors: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry; D006801:Humans; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D014404:Tubulin; D050257:Tubulin Modulators; D006655:Histone Deacetylases; D003078:Colchicine
keywords: Colchicine; Dual inhibitor; HDAC; Hybrid; Tubulin