Synthesis and Hemostatic Activity of New Amide Derivatives (2022)
Eight dipeptides containing antifibrinolytic agents (tranexamic acid, aminocaproic acid,4-(aminomethyl)benzoic acid, and glycine—natural amino acids) were synthesized in a three-stepprocess with good or very good yields. DMT/NMM/TsO− (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate) was used as a coupling reagent. Hemolysis tests wereused to study the effects of the dipeptides on blood components. Blood plasma clotting tests wereused to examine their effects on thrombin time (TT), prothrombin time (PT), and the activated partialthromboplastin time (aPTT). The level of hemolysis did not exceed 1%. In clotting tests, TT, PT, andaPTT did not differentiate any of the compounds. The prothrombin times for all amides 1–8 weresimilar. The obtained results in the presence of amides 1–4 and 8 were slightly lower than for theother compounds and the positive control, and they were similar to the results obtained for TA. In thecase of amide 3, a significantly decreased aPTT was observed. The aPTTs observed for plasma treatedwith amide 3 and TA were comparable. In the case of amide 6 and 8, TT values significantly lowerthan for the other compounds were found. The clot formation and fibrinolysis (CFF) assay was usedto assess the influence of the dipeptides on the blood plasma coagulation cascade and the fibrinolyticefficiency of the blood plasma. In the clot formation and fibrinolysis assay, amides 5 and 7 wereamong the most active compounds. The cytotoxicity and genotoxicity of the synthesized dipeptideswere evaluated on the monocyte/macrophage peripheral blood cell line. The dipeptides did notcause hemolysis at any concentrations. They exhibited no significant cytotoxic effect on SC cells anddid not induce significant DNA damage.
Keywords: nauki medyczne