Ribonucleotide Reductase Inhibitors for AIDS Therapy

We will develop a series of Ribonucleotide reductase inhibitors for the treatment of retrovirus (AIRibonucleotide reductase catalyzes the reductive conversion of ribonucleotides to deoxyribonucleotidapproach is the premise that the quantity of deoxynucleotides can be made deficient for the synthesiproviral DNA by inhibiting deoxynucleotide synthesis. In addition, a ribonucleotide reductase inhibiendogenous deoxynucleotide pools and thereby increase the effectiveness of antiretroviral deoxynucleAZT, ddC, and ddl. In order to determine the potential efficacy for HIV treatment, the leading two ctrimidox and didox, will be evaluated singly and in combination with anti-AIDS dideoxynucleosides AZHIV infected human (hu)-PBL-SCID mouse model. In support of the animal model studies, exploratory inHIV infected PBL cells, especially against resistant strains, will be performed using the drugs singcombination with dideoxynucleosides. Didox has been in human clinical phase l trials for cancer treasuggest it will have an acceptable toxicity profile.