Bruzgo I

Synthesis and activity of amides of tripeptides as potential urokinase inhibitors

Eleven peptides of the general formula H-d-Ser-Ala-Arg-NH-X, where X = (CH2)n-NH2, n = 2–9, (CH2)m-OH, m = 2–4, were obtained and tested for their effect on the amidolytic activities of urokinase, thrombin, trypsin, plasmin, t-PA, and kallikrein. H-d-Ser-Ala-Arg-NH-(CH2)5-NH2 inhibited urokinase with a Ki value of 6.3 μM.

Synthesis and activity of N-sulfonylamides of tripeptides as potential urokinase inhibitors.

Twelve peptides of the general X-SO(2)-D-Ser-Ala-Arg-OH formula (where X = methyl, phenyl, α-tolyl, p-tolyl, 4-methylbenzyl, 1-naphtyl, 2-naphtyl, 4-chlorophenyl, 4-bromophenyl, 2-mesityl, 2,4,6-triisopropylphenyl, 4-acetamidophenyl) were obtained and tested for their effect on the amidolytic activities of urokinase, thrombin, trypsin, plasmin, t-PA and kallikrein. 2,4,6-triisopropylphenyl-SO(2)-D-Ser-Ala-Arg-OH was the most selective inhibitor of urokinase and α-tolyl-SO(2)-D-Ser-Ala-Arg-OH was the most active inhibitor of uPA with K(i) value 24 µM. The compounds were tested for their in vitro antitumour activity in the following human breast cancer cells: standard MCF-7 and estrogen-independent MDA-MB-231. Four of the synthesized peptides showed cytotoxic effects against MDA-MB-231 cell lines in the range from 2.9 to 8.5 µM. The examined compound did not influence to MCF-7 cancer cells. The synthesized peptides were nontoxic to pigs erythrocytes.

Carbocyclic potential DNA minor groove binders and their biological evaluation

The biological evaluation of carbocyclic minor groove binders 1–6 is described. The cytotoxicity of the obtained compounds was tested on MDA-MB-231 breast cancer cells. The mechanism of action of compounds 1–6 was studied employing the topoisomerase I/II inhibition assay and ethidium displacement assay using pBR322. Determination of association constants was done using calf thymus DNA, T4 coliphage DNA, poly(dA-dT)2, and poly(dG-dC)2. The effect of compounds 1–6 on the amidolytic activity of plasmin, trypsin, thrombin, and urokinase was also examined.

The effect of ε-aminocaproyl-S-benzyl-L-cysteine on the t-PA activity of human saliva

PURPOSE The aim of this work was to study the effect of the synthetic antifibrinolytics: ε-aminocaproic acid (EACA), tranexamic acid (AMCHA) and ε-aminocaproyl-S-benzyl-L-cysteine (H-EACA-S-Bzl-L-Cys-OH) on the fibrinolytic activity of saliva in order to obtain new data on the activity of saliva tissue plasminogen activator (t-PA). MATERIAL AND METHODS Saliva samples were obtained from healthy volunteers. Saliva, precipitate and supernatant were tested 1hr, 4 hrs and 6hrs after collection. The effect of the synthetic antifibrinolytics was examined with the use of the clot lysis time determination. RESULTS All examined compounds inhibited the fibrinolytic activity of saliva 1hr after collection. H-EACA-S-Bzl-L-Cys-OH was the most active inhibitor. After 6 hours in room temperature only this compound showed a certain possibility to prolong the clot lysis time. CONCLUSIONS The obtained results may indicate the possibility of the difference in specificity between the activities of t-PA of saliva and recombinant tissue plasminogen activator activities. It may explain the unexpected high inhibitory activity of H-EACA-S-Bzl-L-Cys-OH in our study.