2-Amidino analogs of glycine-amiloride conjugates: Inhibitors of urokinase-type plasminogen activator

Archna P. Massey, William R. Harley, Nagarekha Pasupuleti, Fredric A. Gorin, Michael H Nantz

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2635-2639
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number7
DOIs
StatePublished - Apr 1 2012

Keywords

  • Lactate dehydrogenase
  • Plasminogen activator inhibitor protein-1
  • Tissue plasminogen activator
  • Urokinase-type plasminogen activator
  • Urokinase-type plasminogen activator receptor

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Fingerprint Dive into the research topics of '2-Amidino analogs of glycine-amiloride conjugates: Inhibitors of urokinase-type plasminogen activator'. Together they form a unique fingerprint.

  • Cite this