Adenine and Deazaadenine Nucleoside and Deoxynucleoside Analogues: Inhibition of Viral Replication of Sheep MVV (In Vitro Model for HIV) and Bovine BHV-1

Abstract

A series of N 6-cycloalkyl-2′,3′-dideoxyadenosine derivatives has been prepared by coupling of 2,6-dichloropurine to protected 2,3-dideoxyribose, followed by reaction with appropriate cycloalkylamines. Synthesized compounds, along with other purine nucleoside analogues previously synthesized in our laboratory, have been tested for their antiviral activity against Bovine herpesvirus 1 (BHV-1) and sheep Maedi/Visna Virus (MVV), the latter being an in vitro and in vivo model of Human Immunodeficiency Virus (HIV). All compounds showed good antireplicative activity against MVV, with the N 6-cycloheptyl-2′,3′-dideoxyadenosine ( 5b) being the most active [effective concentration (EC 50) causing 50% reduction of cytopatic effects (CPE)=27 nM]. All compounds showed also a from low to very low cell toxicity, resulting in a cytotoxic dose 50 (CD 50)/EC 50 ratio in some cases higher than 1000.