Novel potential agents for human cytomegalovirus infection: Synthesis and antiviral activity evaluation of benzothiadiazine dioxide acyclonucleosides

The first acyclonucleosides based on the benzothiadiazine dioxide system we re synthesized following the silylation procedure. Several acyclic moieties , including acetoxyethoxymethyl, benzyloxymethyl, and propargyloxymethyl gr oups, were introduced. Two synthetic strategies were designed to selectivel y obtain the N-1 or N-3 derivatives. Lipase-mediated deacylation was used f or the deprotection of the acyclonucleosides. Some of the benzothiadiazine dioxide acyclonucleosides, in particular 16, proved active against human cy tomegalovirus (CMV) at concentrations slightly higher than that found for g anciclovir [50% inhibitory concentration (IC50) = 3.5-3.7 mu g/mL, cytotoxi city (CC50) greater than or equal to 40 mu g/mL, MCC 20 mu g/mL]. Additiona lly, compound 16 inhibited the replication of human immunodeficiency virus type 1 (HTV-1) and HTV-2 in CEM cells at concentrations that were 5-fold lo wer than its cytotoxic concentration.