title: Synthesis and Comparative Study of Anti-Adenoviral Activity of 6-Azacytidine and Its Analogues.
abstract: This paper presents the results of synthesis and study of cytotoxicity and the anti-adenoviral activity of new N4-derivatives of 6-azacytidine and its α-L-glycopyranosyl analogues obtained by the simplified one-pot version of the silyl condensation method. The resulting acylated 4-methylmercapto-1,2,4-triazin-3(2Н)-one glycosides then underwent the amination and/or ammonolysis to provide 6-azacytidine glycoside analogues (2-6, 12, 15, 17) and compounds with modifications at both base and sugar fragments (11, 15). The evaluation of cytotoxicity and antiviral activity of new compounds against AdV5 showed high selectivity indexes for N4-methyl-6-azacytidine (2) and N,O-tetraacetyl-6-azacytidine (8). High anti-adenoviral activity of N4-methyl-6-azacytidine as well as very low cytotoxicity may suggest its further investigation as potential compound for the therapy of AdV infection.
authors.affiliation: a Institute of Molecular Biology and Genetics, National Academy of Sciences , Kyiv , Ukraine.
authors.forename: Inna
authors.initials: I
authors.lastname: Alexeeva
authors.forename: Lydia
authors.initials: L
authors.lastname: Nosach
authors.forename: Larisa
authors.initials: L
authors.lastname: Palchykovska
authors.forename: Lyubov
authors.initials: L
authors.lastname: Usenko
authors.forename: Olga
authors.initials: O
authors.lastname: Povnitsa
mesh_terms: D000256:Adenoviridae / Q000187:drug effects*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006801:Humans; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001374:Azacitidine; C040881:6-azacytidine
keywords: 6-azacytidine; antiviral agents; human adenovirus; nucleoside analogues