Activity and molecular modeling of a new small molecule active against NNRTI-resistant HIV-1 mutants

In this preliminary study we report the antiviral screening of triazolo[4,5-g]quinoline derivatives (compounds 1–6). 4,9-Dihydrotriazolo[4,5-g]quinoline-1-oxide (1) stood out as a new, small molecule endowed with a selective, promising activity in cell-based assays against HIV-1wt and clinically relevant NNRTI resistant mutants. In order to identify the molecular target, compound 1 was assayed in enzyme assay against the HIV-1wt RT. The molecular modeling strategy adopted yielded a rationale, in terms of molecular interactions and free energy of binding, for the possible reasons of the activity of this compound against NNRTI-resistant HIV-1 mutants with the RT isoforms K103N and Y181C.

Graphical abstractBy cell-based screenings, enzyme assay against HIV-1wt RT and molecular modeling studies, 4,9-dihydrotriazolo[4,5-g]quinoline-1-oxide (1) stood out as a new, small molecule endowed with a selective promising anti-HIV activity.Figure optionsDownload full-size imageDownload as PowerPoint slide