THE FIAU DERIVATIVE (2'S)-2'-DEOXY-2'-C-METHYL-5-IODOURIDINE (SMIU) IS A NOVEL, LESS CYTOTOXIC AND POTENT ANTI-HSV AND ANTI-VZV AGENT

In this study, the anti-herpetic activities of novel 2'-methyl nucleos ide analogues which were substituted at the 5 position of the pyrimidi ne with a halogen were investigated. The 2'-fluoro-5-iodo-aracytosine (FIAC) congeners (2'S)-2'-deoxy-2'-C-methylcytidine which were substit uted with Br or I at the 5 position (SMBC or SMIC); and 2'-fluoro-5-io do-arauridine (FIAU) congeners (2'S)-2'-deoxy-2'-C-methyluridine which were substituted with Sr or I at the 5 position (SMBU or SMIU), prove d to have potent antiviral activities against herpes simplex virus typ e-1 (HSV-1) and varicella-zoster virus (VZV) but not against herpes si mplex virus type -2 (HSV-2). SMIU has a higher selective index against HSV-1 than FIAU, and both SMIC and SMIU showed higher inhibitory effe cts against VZV replication than aciclovir. The four effective compoun ds were not inhibitory to a thymidine kinase (TK)-negative HSV-1 strai n, and this result indicates that phosphorylation of the compounds by HSV or VZV -TK is necessary for the activation of these compounds.