Abstract
The relative non-toxicity of the diuretic amiloride, coupled with its selective inhibition of the protease urokinase plasminogen activator (uPA), makes this compound class attractive for structure-activity studies. Herein we substituted the C(2)-acylguanidine of C(5)-glycyl-amiloride with amidine and amidoxime groups. The data show the importance of maintaining C(5)-hydrophobicity. The C(5)-benzylglycine analogs containing either C(2)-acylguanidine or amidine inhibited uPA with an IC(50) ranging from 3 to 7 μM and were cytotoxic to human U87 malignant glioma cells.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amidines / chemical synthesis*
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Amidines / pharmacology
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Amiloride / analogs & derivatives*
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Amiloride / chemical synthesis*
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Amiloride / pharmacology
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Cell Survival / drug effects
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Drug Screening Assays, Antitumor
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Glycine / analogs & derivatives*
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Glycine / chemical synthesis*
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Glycine / pharmacology
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Humans
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Hydrophobic and Hydrophilic Interactions
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Serine Proteinase Inhibitors / chemical synthesis*
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Serine Proteinase Inhibitors / pharmacology
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Structure-Activity Relationship
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Tissue Plasminogen Activator / metabolism
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Urokinase-Type Plasminogen Activator / antagonists & inhibitors*
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Urokinase-Type Plasminogen Activator / metabolism
Substances
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Amidines
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Antineoplastic Agents
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Serine Proteinase Inhibitors
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Amiloride
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Tissue Plasminogen Activator
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Urokinase-Type Plasminogen Activator
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Glycine