Abstract:
:Recently we found that 1-methyldodecanoylindole-2-carboxylic acid (1) and 1-[2-(4-carboxyphenoxy)ethyl]-3-dodecanoylindole-2-carboxylic acid (4) were inhibitors of the cytosolic phospholipase A2alpha (cPLA2alpha)-mediated arachidonic acid release in calcium ionophore A23187-stimulated human platelets with IC50-values of 4.8 microM (1) and 0.86 microM (4). We have now replaced the 3-acyl residue of these compounds by alkylated sulfinyl-, sulfony-, sulfinamoyl-, sulfamoyl-, carbonylamino-, or carbonylaminomethyl-substituents. Structure-activity relationship studies revealed that the pronounced cellular activity of 4 strongly depends on the presence of the 3-acyl moiety. Surprisingly, when testing 4 and its derivatives in an assay with the isolated cPLA2, none of these compounds showed an inhibitory potency at 10 microM indicating that they do not inhibit cPLA2alpha in the cells by a direct interaction with the active site of the enzyme.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Ghasemi A,Elfringhoff AS,Lehr Mdoi
10.1080/14756360500228338keywords:
subject
Has Abstractpub_date
2005-10-01 00:00:00pages
429-37issue
5eissn
1475-6366issn
1475-6374journal_volume
20pub_type
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