Effect of acyclic nucleoside phosphonates on the HIV-1 integrase in vitro.

Integrase (IN) is an essential enzyme in the human immunodeficiency virus type-1 (HIV-1) replication cycle and, thus, a potential target for chemotherapeutic agents. Because various nucleotide analogues have been reported to inhibit IN in vitro, we investigated the effect of acyclic nucleoside phosphonates. Both unphosphorylated and diphosphorylated derivatives were inhibitory to IN at concentrations ranging between 60 and 800 microM, with diphosphorylated derivatives being 5- to 8-fold more potent than unphosphorylated counterparts.