Abstract
The antiproliferative activity on ovarian cancer (SK-OV-3) cells of a series of triazole-bridged combretastatin analogues (37, 38, 40-43) containing dihalogenation of the A-ring is reported, and compared with their trimethoxy analogues (5, 15, 39). It was found that dihalogenation with either bromine or iodine was a tolerated modification when compared to the parent compound combretastatin (CA-4, 1) and had less effect than B-ring modification on potency. These compounds exhibited G(2)/M arrest, and maintained antitubulin activity. Further assays on human umbilical vein endothelial cells (HUVECs) demonstrated the potential antivascular effects of these triazoles. Of particular note was a 3,5-diiodo-4-methoxyaryl triazole (43) which had promising 7-fold selectivity for HUVECs over ovarian cancer cells.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacokinetics
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Angiogenesis Inhibitors / pharmacology
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / pharmacology
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Cell Cycle / drug effects
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Cell Growth Processes / drug effects
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Cell Line, Tumor
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Female
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Human Umbilical Vein Endothelial Cells / cytology
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Human Umbilical Vein Endothelial Cells / drug effects*
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Human Umbilical Vein Endothelial Cells / metabolism*
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Humans
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Models, Molecular
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / metabolism
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Stilbenes / chemistry*
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Stilbenes / pharmacokinetics
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Stilbenes / pharmacology*
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Structure-Activity Relationship
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Triazoles / chemistry*
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Triazoles / pharmacokinetics
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Triazoles / pharmacology*
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Tubulin / metabolism
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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Stilbenes
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Triazoles
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Tubulin
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combretastatin A-1