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2‐Substituted 6‐(Het)aryl‐7‐deazapurine Ribonucleosides: Synthesis, Inhibition of Adenosine Kinases, and Antimycobacterial Activity
Author(s) -
Malnuit Vincent,
Slavětínská Lenka Poštová,
Nauš Petr,
Džubák Petr,
Hajdúch Marián,
Stolaříková Jiřina,
Snášel Jan,
Pichová Iva,
Hocek Michal
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500081
Subject(s) - antimycobacterial , chemistry , adenosine kinase , mycobacterium tuberculosis , substituent , stereochemistry , kinase , adenosine , aryl , nucleotide salvage , biochemistry , tuberculosis , adenosine deaminase , medicine , nucleotide , organic chemistry , alkyl , pathology , gene
A series of 6‐(hetero)aryl‐ or 6‐methyl‐7‐deazapurine ribonucleosides bearing a substituent at position 2 (Cl, F, NH 2 , or CH 3 ) 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.