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

Out of the 41 unique compounds originally screened for anti-HIV-1 activity, one compound, 170 quinol-type 2´-deoxy-8-azaBINOL ether B#24, stands out with selective antiviral activity and a 171 favorable selectivity index. Small changes to its structure, including moving the isopropyl ether 172 substituent to the naphthyl ring system (B#59), or the introduction of an additional aromatic ring-173 bound nitrogen atom (B#57), results in drastically reduced antiviral activity. While the deoxy-8-174 azaBINOL carbamate derivatives B#43 and B#60 do exhibit antiviral activity in the phenotypic 175 assays, they also show significant cytotoxicity and therefore their apparent antiviral activity is 176 likely due to interference with the cell-based assay. The low micromolar antiviral activity of lead 177 compound B#24 encouraged us to explore its mode-of-action. 178