title: Thrombin inhibitors with lipid peroxidation and lipoxygenase inhibitory activities.
abstract: Vascular oxidative stress, endothelial injury, and thrombosis are intertwined processes that display a synergistic pathological effect in many cardiovascular diseases. Antithrombotic therapy with anticoagulant and/or antiplatelet agents, combined with interventions against vascular oxidative stress and/or inflammation, both boosting endothelial antithrombotic potential, could display a synergistic action in the treatment of thrombosis. Of the compounds 10a-h and 11a-d, shown to possess thrombin inhibitory activity, 11a-d were found to display radical scavenging activity, 10a, 10d, and 10f were demonstrated to inhibit lipid peroxidation of linoleic acid, and 10b and 10h inhibited soybean lipoxygenase. The observed combination of thrombin inhibition with lipid peroxidation and/or lipoxygenase inhibitory activity makes compounds 10 and 11 interesting candidates for further investigations towards multiple antithrombotic drugs.
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Miloš
authors.initials: M
authors.lastname: Ilić
authors.forename: Christos
authors.initials: C
authors.lastname: Kontogiorgis
authors.forename: Dimitra
authors.initials: D
authors.lastname: Hadjipavlou-Litina
authors.forename: Janez
authors.initials: J
authors.lastname: Ilaš
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
mesh_terms: D019787:Linoleic Acid / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects*; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013025:Glycine max / Q000201:enzymology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D016859:Lipoxygenase Inhibitors; D019787:Linoleic Acid; D008084:Lipoxygenase; D013917:Thrombin