Aryl-7-deazapurine Nucleosides and Their Biological Activity

Abstract

Aryl-7-deazapurine nucleosides possess interesting cytotoxic and antiparasitic activities. This review summarizes synthetic approaches to introduction of aryl group to the nucleobase of 7-deazapurine nucleosides. Biological activities of 7-deazapurine nucleosides, their mode of action and structure-activity relationships are discussed. The most promising compounds with cytotoxic activities against cancer cells are 6-hetaryl-7-deazapurine ribonucleosides substituted with a 5-membered heterocycle and 7‑hetaryl-7-deazaadenosines with the same substituents. A new complex mode of action was described for 7‑(2‑thienyl)-7-deazaadenosine (AB61). Significant antitrypanosomal activities both in vitro and in vivo were discovered among 7-phenyl-7-deazaadenine nucleosides. 6‑Hetaryl-7-deazapurine ribonucleosides with bulky heterocyclic substituents in position 6 strongly and selectively inhibit mycobacterial adenosine kinase. Due to their diverse application possibilities and relatively easy synthesis, aryl-7-deazapurine nucleosides represent a source of interesting new compounds for further research by medicinal chemists.