Unsaturation: An Important Structural Feature to Nucleosides’ Antiviral Activity

Stella      Manta; Christos      Kiritsis; Athina      Dimopoulou; Vanessa      Parmenopoulou; Nikolaos      Kollatos; Andrew      Tsotinis; Dimitri      Komiotis

doi:10.2174/22113525113119990106

Abstract

In the search of effective, selective and nontoxic antiviral agents, a variety of nucleoside analogues have been synthesized, with different functionalities in the carbohydrate moiety and/or the heterocyclic base. Nucleoside analogues bearing double or triple bonds are recognized as an important class of biologically active compounds and appear to be prominent drugs in the management of several viral infections, including HSV, HIV, HBV, HCV and HCMV. Currently, unsaturated nucleoside mimetics, such as stavudine, abacavir and entecavir have been approved for the treatment of viral infections, while elvucitabine and β-L-2´-F-d4C are in clinical trials. The purpose of this review is to give an update of the recent developments on nucleosides and nucleoside analogues with unsaturation, in both cyclic and acyclic forms, which possess promising therapeutic potential, mainly antiviral. It covers analogues with ring sizes from three to six and provides useful data, aiming at enhancing chemical reactivity as a result of the sugar and base conformations.

Keywords: Acyclic, antiviral, base modified, carbocyclic, exomethylene, TSAO, unsaturated nucleosides.