Biological Evaluation of Molecules of the azaBINOL Class as Antiviral Agents: Specific Inhibition of HIV-1 RNase H Activity by 7-Isopropoxy-8-(naphth-1-yl)quinoline

Ross D. Overacker; Somdev Banerjee; George F. Neuhaus; Selena Milicevic Sephton; Alexander Herrmann; James A. Strother; Ruth Brack-Werner; Paul R. Blakemore; Sandra Loesgen

shows unoptimized low micromolar activity (4-9 µM range) in an HIV single round infectivity 99 assay as well as in fully infectious viral assays with low cytotoxicity and a selectivity index 100 of 14. 101 typed particles with differing tropism including HXB2, YU2, and 89.6 ( Table 1 ). All six of the 148 azaBINOL compounds showed similar activities across all viral variants. Quinol-type 2´-deoxy-149 8-azaBINOL ether B#24 in particular showed low micromolar HIV-1 neutralization against each 150 of the strains tested with activity similar to other antiviral drugs such as abacavir. 34 Although the 151 naphthol-type 2-deoxy-8-azaBINOL ether B#59 did show minor antiviral activity at high 152 concentrations, its IC50 was greater than the concentrations tested and significantly larger in 153 comparison to the closely related quinol-type ether B#24, which has an IC50 value of 4 -8 µM. 154