Synthesis and Activity of N-Sulfonylamides of Tripeptides as Potential Urokinase Inhibitors

Twelve peptides of the general X-SO2-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-SO2-D-Ser-Ala-Arg-OH was the most selective inhibitor of urokinase and α-tolyl-SO2-D-Ser-Ala-Arg-OH was the most active inhibitor of uPA with Ki 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 pig's erythrocytes.