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.
Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Publication types
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Evaluation Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology
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Cell Cycle / drug effects
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Cell Proliferation / drug effects
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Colchicine / chemistry*
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Colchicine / pharmacology*
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Drug Design*
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Drug Screening Assays, Antitumor
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HCT116 Cells
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Histone Deacetylase Inhibitors / chemical synthesis*
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Histone Deacetylase Inhibitors / pharmacology*
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Histone Deacetylases / chemistry
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Humans
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Structure-Activity Relationship
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Tubulin / chemistry
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Tubulin Modulators / chemical synthesis*
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Tubulin Modulators / pharmacology*
Substances
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Antineoplastic Agents
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Histone Deacetylase Inhibitors
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Tubulin
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Tubulin Modulators
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Histone Deacetylases
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Colchicine