Thioredoxins (Trx) are ubiquitous multifunctional low-molecular weight proteins that together with thioredoxin reductases (TrxR) participate in the maintenance of protein thiol homeostasis in NADPH-dependent reactions. An increasing number of data reveal that the Trx−TrxR system is an attractive target for anticancer therapies. Based on our studies on synthesis on the successful combination of mutlicomponent reactions with enzymatic transformations to the synthesis of bioactive tripeptide mimetics [1,2,3], we have elaborated a new and simple synthetic approach employing Ugi reaction to synthesize several new inhibitors of this system. The influence of various electrophilic fragments of this new class of compounds on the inhibition of the Trx−TrxR system was evaluated. As a result, a new compound SK053, which inhibits the activity of the Trx−TrxR system and exhibits antitumor activity, was obtained. Biologic analyses revealed that SK053 inhibits induction of NF-κB and AP-1 and decreases H₂O₂ scavenging capacity in tumor cells.

The results of our studies on the successful application of mutlicomponent Ugi reactions to the synthesis of bioactive tripeptide mimetics, will be presented [4].

[1] Szymanski, W., Ostaszewski, R.; Tetrahedron: Asymmetry, 17, 2667-2671, 2006.

[2] Mroczkiewicz M., Ostaszewski R., Tetrahedron, 65, 4025-4034, 2009.

[3] M. Mroczkiewicz, K. Winkler, D. Nowis, G. Placha, J. Golab,R. Ostaszewski, J. Med. Chem., 53, 2010, 1509–1518.

[4] S. Kłossowski , A. Muchowicz, M. Firczuk, M. Świech, A. Redzej, J. Golab, R. Ostaszewski, J. Med Chem. 55, 2012, 55-67.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/28032 must be provided.

1. Studies towards stereoselective bionanocatalysis on gold nanoparticles
2. Synthesis of marker compounds for detailed explanation the mechanism of anticancer activity of peptidomimetics with β-acyloxymethacrylic fragment
3. Synthesis and biological evaluation of new inhibitors of thioredoxin - thioredoxin reductase.
4. Chemoenzymatic approach to the synthesis of bioactive tripeptide mimetics for treatment of cancer
5. Synthesis of novel, thioredoxin - thioredoxin reductase inhibitors
6. Selective monoacylation of alkane-α,ω-diols using crude acetone powders of animal tissues
7. Synthesis of novel, peptidic kinase inhibitors with cytotoxic activity
8. First attempts at the enzyme-promoted hydrolysis of N-acyl phosphonoamides
9. STUDIES ON THE SYNTHESIS AND BIOLOGICAL ACTIVITY OF COLCHICINE ANALOGUES