| Abstract
| - The first acyclonucleosides based on the benzothiadiazine dioxide system were synthesizedfollowing the silylation procedure. Several acyclic moieties, including acetoxyethoxymethyl,benzyloxymethyl, and propargyloxymethyl groups, were introduced. Two synthetic strategieswere designed to selectively obtain the N-1 or N-3 derivatives. Lipase-mediated deacylationwas used for the deprotection of the acyclonucleosides. Some of the benzothiadiazine dioxideacyclonucleosides, in particular 16, proved active against human cytomegalovirus (CMV) atconcentrations slightly higher than that found for ganciclovir [50% inhibitory concentration(IC50) = 3.5−3.7 μg/mL, cytotoxicity (CC50) ≥ 40 μg/mL, MCC = 20 μg/mL]. Additionally,compound 16 inhibited the replication of human immunodeficiency virus type 1 (HIV-1) andHIV-2 in CEM cells at concentrations that were 5-fold lower than its cytotoxic concentration.
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