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

Integrase (IN) is an essential enzyme in the human immunodeficiency virus t ype-1 (HIV-1) replication cycle and, thus, a potential target for chemother apeutic agents. Because various nucleotide analogues have been reported to inhibit IN in vitro, we investigated the effect of acyclic nucleoside phosp honates. Both unphosphorylated and diphosphorylated derivatives were inhibi tory to IN at concentrations ranging between 60 and 800 mu M, with diphosph orylated derivatives being 5- to g-fold more potent than unphosphorylated c ounterparts.