Abstract
Histone deacetylases (HDACs) inhibitors have multiple effects targeting the cancer cells and have become one of the promising cancer therapeutics with possibly broad applicability. Combination of HDAC inhibitors with the cytotoxic fluorouracil (5-FU) showed additive and synergistic effects both in vitro and in vivo. To explore the possibility in cancer therapy of a bivalent agent that combines two bioactive groups within a single molecular architecture, we designed and synthesized new dual-acting compounds by combining the bioactive fragment of MS-275, a clinical HDACs inhibitor, with cytotoxic agent 5-FU. The target compounds 9a and 9b showed comparable HDACs inhibition with MS-275 and moderate antiproliferative acitivities against six cancer cells lines.
Publication types
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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 / chemistry
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Antineoplastic Agents / pharmacology*
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Benzamides / chemical synthesis
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Benzamides / chemistry
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Benzamides / pharmacology*
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Fluorouracil / analogs & derivatives*
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Fluorouracil / chemical synthesis
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Fluorouracil / chemistry
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Fluorouracil / pharmacology
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HeLa 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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Molecular Docking Simulation
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Pyridines / pharmacology
Substances
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(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl) methyl-(4-((2-aminophenyl)carbamoyl)phenyl)carbamate
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(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl-4-((2-aminophenyl)carbamoyl)benzylcarbamate
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Antineoplastic Agents
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Benzamides
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Histone Deacetylase Inhibitors
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Pyridines
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entinostat
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Fluorouracil