Synthesis of marker compounds for detailed explanation the mechanism of anticancer activity of peptidomimetics with β-acyloxymethacrylic fragment

Szymon Kłossowski 1Małgorzata Firczuk 2Angelika Muchowicz 2Jakub Golab 2Ryszard Ostaszewski 1

1. Instytut Chemii Organicznej Polskiej Akademii Nauk (ICHOPAN), Kasprzaka 44/52, Warszawa 01-224, Poland
2. Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland

Abstract

During recent studies on development new inhibitor of thioredoxin system inhibitors, the new class of β-acyloxyamides I has been found. Studied peptidomimetics exhibited interesting biological properties and were very potent anticancer agents either in vitro (in cellular assays) or in vivo (mice model). [1,2]

Detailed mechanistic studies indicated, however, that compound I activates apoptotic pathways not only by inhibiting the thioredoxin system. To establish mechanism of action of new compounds in a cell, we developed marker compounds containing fluorescent fragments as well as biotinylated compounds 1 and 2. Here, we will present the proposed methodology as well as the results of studies on the synthesis of compounds 1 and 2.

[1]: Klossowski, S., Muchowicz, A., Firczuk, M., Swiech, M., Redzej, A., Golab, J., Ostaszewski, R., J. Med. Chem. 2012, 55, 1, p. 55 - 67

[2]: Ostaszewski, R., Klossowski, S., Szokalska, A., Swiech, M., Ziuzia I., Golab, J., Patent App. PK/1081/AG

 

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Presentation: Poster at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Szymon Kłossowski
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2012-03-14 09:38
Revised:   2012-05-10 09:29