title: 2-Substituted 6-(Het)aryl-7-deazapurine Ribonucleosides: Synthesis, Inhibition of Adenosine Kinases, and Antimycobacterial Activity.
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.
authors.affiliation: 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.
authors.forename: Vincent
authors.initials: V
authors.lastname: Malnuit
authors.affiliation: 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.
authors.forename: Lenka Poštová
authors.initials: LP
authors.lastname: Slavětínská
authors.affiliation: 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.
authors.forename: Petr
authors.initials: P
authors.lastname: Nauš
authors.affiliation: Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Hněvotínská 5, 77515 Olomouc (Czech Republic).
authors.forename: Petr
authors.initials: P
authors.lastname: Džubák
authors.affiliation: Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Hněvotínská 5, 77515 Olomouc (Czech Republic).
authors.forename: Marián
authors.initials: M
authors.lastname: Hajdúch
authors.affiliation: Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské nám. 7, 70200 Ostrava (Czech Republic).
authors.forename: Jiřina
authors.initials: J
authors.lastname: Stolaříková
authors.affiliation: 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Snášel
authors.affiliation: 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.
authors.forename: Iva
authors.initials: I
authors.lastname: Pichová
authors.affiliation: 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. hocek@uochb.cas.cz.|Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12843 Prague 2 (Czech Republic). hocek@uochb.cas.cz.
authors.forename: Michal
authors.initials: M
authors.lastname: Hocek
mesh_terms: D000248:Adenosine Kinase / Q000037:antagonists & inhibitors*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D011687:Purines / Q000737:chemistry*; D012263:Ribonucleosides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C512929:7-deazapurine; D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D011687:Purines; D012263:Ribonucleosides; D000248:Adenosine Kinase
keywords: antimycobacterial agents; cytostatics; nucleosides; purines; pyrrolopyrimidines