2‐Substituted 6‐(Het)aryl‐7‐deazapurine Ribonucleosides: Synthesis,Inhibition of Adenosine Kinases,and Antimycobacterial Activity |
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Authors: | Dr Vincent Malnuit Dr Lenka Po?tová Slavětínská Dr Petr Nau? Dr Petr D?ubák Prof Marián Hajdúch Dr Ji?ina Stola?íková Dr Jan Sná?el Dr Iva Pichová Prof?Dr Michal Hocek |
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Affiliation: | 1. Institute of Organic Chemistry and Biochemistry, Academy of Science Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nám. 2, 16610 Prague 6 (Czech Republic) http://www.uochb.cas.cz/hocekgroup;2. Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Hněvotínská 5, 77515 Olomouc (Czech Republic);3. Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské nám. 7, 70200 Ostrava (Czech Republic);4. Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12843 Prague 2 (Czech Republic) |
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Abstract: | A series of 6‐(hetero)aryl‐ or 6‐methyl‐7‐deazapurine ribonucleosides bearing a substituent at position 2 (Cl, F, NH2, or CH3) were prepared by cross‐coupling reactions at position 6 and functional group transformations at position 2. Cytostatic, antiviral, and antimicrobial activity assays were performed. The title compounds were observed to be potent and selective inhibitors of Mycobacterium tuberculosis adenosine kinase (ADK), but not human ADK; moreover, they were found to be non‐cytotoxic. The antimycobacterial activities against M. tuberculosis, however, were only moderate. The reason for this could be due to either poor uptake through the cell wall or to parallel biosynthesis of adenosine monophosphate by the salvage pathway. |
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Keywords: | antimycobacterial agents cytostatics nucleosides purines pyrrolopyrimidines |
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