Adenine and deazaadenine nucleoside and deoxynucleoside analogues: inhibition of viral replication of sheep MVV (in vitro model for HIV) and bovine BHV-1.
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.
Salvatori
Daniela
D
Dipartimento di Scienze Veterinarie, Università di, Camerino, Italy.
Volpini
Rosaria
R
Vincenzetti
Silvia
S
Vita
Alberto
A
Costanzi
Stefano
S
Lambertucci
Catia
C
Cristalli
Gloria
G
Vittori
Sauro
S
D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016048:Dideoxyadenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006678:HIV; D007242:Herpesvirus 1, Bovine / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D013329:Structure-Activity Relationship; D014372:Tubercidin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D014790:Visna-maedi virus / Q000187:drug effects* / Q000502:physiology
D016048:Dideoxyadenosine; D014372:Tubercidin