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 language | English (US) |
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Pages (from-to) | 2635-2639 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 22 |
Issue number | 7 |
DOIs | |
State | Published - 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