2‐Substituted 6‐(Het)aryl‐7‐deazapurine Ribonucleosides: Synthesis, Inhibition of Adenosine Kinases, and Antimycobacterial Activity. Issue 6 (16th April 2015)

• Record Type: Journal Article
• Authors: Malnuit, Vincent; Slavětínská, Lenka Poštová; Nauš, Petr; Džubák, Petr; Hajdúch, Marián; Stolaříková, Jiřina; Snášel, Jan; Pichová, Iva; Hocek, Michal
• Is Part Of: ChemMedChem. Volume 10:Issue 6(2015:Jun.)
• Page Start: 1079
• Page End: 1093
• Publication Date: 2015-04-16
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201500081
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 <italic>Mycobacterium tuberculosis</italic> adenosine kinase (ADK), but not human ADK; moreover, they were found to be non‐cytotoxic. The antimycobacterial activities against <italic>M. tuberculosis</italic>, 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.</p> </abstract>