| Abstract |
In the context of the novel type of cytostatics (6-hetaryl-7-deazapurine nucleosides) recently developed in our laboratory, the project will deal with the synthesis of other derivatives and analogues derived from this structural motif and with biological activity screening (cytostatic effect, inhibition of adenosine kinases). Several approaches will be used in parallel: (structure variation of the lead, (ii) rational design based on docking to active site of enzymes and (iii) dynamic combinatorial libraries.
Key reference:
1. Nauš, P.; Pohl, R.; Votruba, I.; Džubák, P.; Hajdúch, M.; Ameral, R.; Birkuš, G.; Wang, T.; Ray, A. S.; Mackman, R.; Cihlar, T.; Hocek, M. "6-(Het)aryl-7-Deazapurine Ribonucleosides as Novel Potent Cytostatic Agents" J. Med. Chem. 2010, 53, 460-470.
2. Spáčilová, P.; Nauš, P.; Pohl, R.; Votruba, I.; Snášel, J.; Zábranská, H.; Pichová, I.; Ameral, R.; Birkuš, G.; Cihlář, T.; Hocek, M. "CycloSal-Phosphate Pronucleotides of Cytostatic 6-(Het)aryl-7-Deazapurine Ribonucleosides: Synthesis, Cytostatic Activity, and Inhibition of Adenosine Kinases" ChemMedChem 2010, 5, 1386–1396.
3. Perlíková, P.; Pohl, R.; Votruba, I.; Shih, R.; Birkuš, G.; Cihlář, T.; Hocek, M. "Phosphoramidate pronucleotides of cytostatic 6-aryl-7-deazapurine ribonucleosides" Bioorg. Med. Chem. 2011, 19, 229-242.
4. Bourderioux, A.; Nauš, P.; Perlíková, P.; Pohl, R.; Pichová, I.; Votruba, I.; Džubák, P.; Konečný, P.; Hajdúch, M.; Stray, K. M.; Wang, T.; Ray, A. S.; Feng, J. Y.; Birkus, G.; Cihlar, T.; Hocek, M. "Synthesis and significant cytostatic activity of 7-hetaryl-7-deazaadenosines" J. Med. Chem. 2011, 54, 5498-5507.
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