Abstract
Designing multitarget drugs have raised considerable interest due to their advantages in the treatment of complex diseases such as cancer. Their design constitutes a challenge in antitumor drug discovery. The present study reports a dual inhibition of tubulin polymerization and HDAC activity. On the basis of 1,1-diarylethylenes ( isoCA-4) and belinostat, a series of hybrid molecules was successfully designed and synthesized. In particular compounds, 5f and 5h were proven to be potent inhibitors of both tubulin polymerization and HDAC8 leading to excellent antiproliferative activity.
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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Cell Proliferation / drug effects
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Chemistry Techniques, Synthetic
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Drug Design*
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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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Histone Deacetylases / chemistry
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Histone Deacetylases / metabolism*
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Humans
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K562 Cells
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Protein Conformation
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Stilbenes / chemical synthesis
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Stilbenes / chemistry*
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Stilbenes / pharmacology*
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Tubulin / chemistry
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Tubulin / metabolism*
Substances
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Antineoplastic Agents
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Histone Deacetylase Inhibitors
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Stilbenes
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Tubulin
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Histone Deacetylases
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fosbretabulin