ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACTIVITIES OF DIDEOXYNUCLEOSIDE PHOSPHOTRIESTER DERIVATIVES IN PRIMARY MONOCYTES MACROPHAGES

Mononucleoside phosphotriester derivatives of dideoxynucleosides, foll owing intracellular enzymatic activation, are likely to liberate their parent B-nucleoside monophosphate. Prodrugs of 3'-azido-2',3'-dideoxy thymidine (AZT), 2'3'-didehydro-2',3'-dideoxythymidine (d4T), 2',3'-di deoxyinosine (ddl) and 2',3'-dideoxyadenosine (ddA) were evaluated for their anti-HIV1 activities in monocyte-derived macrophages, cells whi ch are known to have low levels of nucleoside kinases. Prodrugs were f ound to be much more active, or just as active, as the corresponding d ideoxynucleoside. Furthermore, their selectivity index was enhanced by a factor of 2 to 200.