Abstract
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 pigs erythrocytes.
Keywords: Urokinase inhibitor, low molecular peptide
Protein & Peptide Letters
Title: Synthesis and Activity of N-Sulfonylamides of Tripeptides as Potential Urokinase Inhibitors
Volume: 17 Issue: 10
Author(s): Agnieszka Markowska, Irena Bruzgo, Wojciech Miltyk and Krystyna Midura-Nowaczek
Affiliation:
Keywords: Urokinase inhibitor, low molecular peptide
Abstract: 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 pigs erythrocytes.
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Cite this article as:
Markowska Agnieszka, Bruzgo Irena, Miltyk Wojciech and Midura-Nowaczek Krystyna, Synthesis and Activity of N-Sulfonylamides of Tripeptides as Potential Urokinase Inhibitors, Protein & Peptide Letters 2010; 17 (10) . https://dx.doi.org/10.2174/092986610792231456
DOI https://dx.doi.org/10.2174/092986610792231456 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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