Synthesis and biological activity of dipeptides containing S-hexylcysteine.

Pathological clot formation is the major cause of many serious diseases. A crucial step at the end of the coagulation cascade is the cleavage of soluble fibrinogen to fibrin clot by thrombin. A number of anticoagulants have been assessed clinically. Side effects such as excessive bleeding and difficulties of drug monitoring have led to considerable activity in the search of novel compounds with anticoagulant activity (1,2). During our earlier investigations on antifibrinolytic activity of S-substituted cysteine derivatives, we observed that some of ε-aminocaproil-(S-alkyl)-cysteines in the high concentration (20 mM), instead of the expected prolongation of fibrinolysis time in fibrinolytic test, prevented clot formation. ε-Aminocaproil-(S-hexyl)-cysteine was the most active compound (3). We observed also that glycyl-(S-hexyl)-cysteine shows similar activity in the range of the examined concentration (4). Anticoagulant or fibrinolytic activity of S-substituted cysteine derivatives was not earlier described. The garlic products (γ-glutamyl-S-alkylcysteines) can be an exception (5). In order to explain this unexpected activity of S-hexylL-cysteine derivatives and in the search for new compounds with anticoagulant activity, we obtained eight dipeptides with general formula XGly-(S-hexyl)-L-Cys-Y and XS-hexyl)-L-CysGly-Y, where: X= H, Boc; Y= OH, OMe or OEt and examined their effect on: thrombin-clotting activity determined with the use of fibrinogen and plasma, fibrinolytic activity of plasmin and amidolytic activities of thrombin and plasmin. EXPERIMENTAL