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.

Keywords: antimycobacterial agents; cytostatics; nucleosides; purines; pyrrolopyrimidines.