Comparative Study of the Anti-Human Cytomegalovirus Activities and Toxicities of a Tetrahydrofuran Phosphonate Analogue of Guanosine and Cidofovir

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Abstract
Cidofovir is the first nucleoside monophosphate analogue currently being used for the treatment of human cytomegalovirus (HCMV) retinitis in individuals with AIDS. Unfortunately, the period of therapy with the use of this compound may be limited due to the possible emergence of serious irreversible nephrotoxic effects. New drugs with improved toxicity profiles are needed. The goal of this study was to investigate the anticytomegaloviral properties and drug-induced toxicity of a novel phosphonate analogue, namely, (−)-2-( R )-dihydroxyphosphinoyl-5-( S )-(guanin-9′-yl-methyl) tetrahydrofuran (compound 1), in comparison with those of cidofovir. The inhibitory activities of both compounds on HCMV propagation in vitro were similar against the AD 169 and Towne strains, with 50% inhibitory concentrations ranging from 0.02 to 0.17 μg/ml for cidofovir and P < 0.001) with a drug regimen of 10 mg/kg/day.