Selective inhibition of human immunodeficiency virus type 1 replication by novel fluoroalkylated oligomers in vitro

Several fluoroalkylated oligomers were found to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. Among the test compounds, bis(perfluoro-1,4,7,10-tetramethyl-2,5,8,11-tetraoxatetradecyl+ ++)methacrylic acid oligomer (MAA-HFPO5) emerged as the most potent inhibitor of HIV-1 replication. Its 50% antivirally effective concentration for the IIIB strain was 2.8 mu g/ml, whereas the compound did not affect the growth and viability of mock-infected MT-4 cells at concentrations < or = 100 micrograms/ml. MAA-HFPO5 was also inhibitory to other strains of HIV-1 in various human T-cell systems, including peripheral blood lymphocytes. MAA-HFPO5 inhibited syncytium formation and virus adsorption. The combination of MAA-HFPO5 with either 3'-azido-3'dioxythymidine or dextran sulfate resulted in an additive effect. Thus, fluoroalkylated oligomers are novel HIV-1 inhibitors that warrant further evaluation of their therapeutic potential.