Abstract
A novel class of di-substituted cinnamic hydroxamic acid derivatives containing urea or thiourea unit was designed, synthesized and evaluated as HDAC inhibitors. All tested compounds demonstrated significant HDAC inhibitory activities and anti-proliferative effects against diverse human tumor cell lines. Among them, 7l exhibited most potent pan-HDAC inhibitory activity, with an IC50 value of 130 nM. It also showed strong cellular inhibition against diverse cell lines including HCT-116, MCF-7, MDB-MB-435 and NCI-460, with GI50 values of 0.35, 0.22, 0.51 and 0.48 μM, respectively.
Keywords:
Cinnamic hydroxamaic acid; HDAC; Histone deacetylase; Thiourea; Urea.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cinnamates / chemical synthesis
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Cinnamates / chemistry*
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Cinnamates / 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 / chemistry*
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Histone Deacetylase Inhibitors / pharmacology*
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Humans
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Hydroxamic Acids / chemical synthesis
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Hydroxamic Acids / chemistry*
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Hydroxamic Acids / pharmacology*
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MCF-7 Cells
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Models, Molecular
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Structure-Activity Relationship
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Thiourea / analogs & derivatives
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Thiourea / chemistry
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Thiourea / pharmacology
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Urea / analogs & derivatives
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Urea / chemistry
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Urea / pharmacology
Substances
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Cinnamates
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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cinnamic acid
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Urea
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Thiourea