Antiviral activity and molecular modeling studies on 1H-indole-2,3-diones carrying a naphthalene moiety

We here report the synthesis, structural characterization, and evaluation of the in vitro antiviral effects of a series of 1H-indole-2,3-diones (2a-f) bearing a naphthalene moiety. All 1-(naphthalen-2-ylmethyl)-1H-indole-2,3-diones (2c-f) tested against different herpes simplex viruses (HSVs) were found to be effective at low micromolar levels (EC50=2.3–20.0 µM). Molecular dynamics and docking simulations were performed with compound 2d which exhibited the strongest activity against HSVs and the binding affinities for HSV-1 surface glycoproteins B (gB) and D (gD) were calculated. Moreover, 5-bromo-1-(naphthalen-1-ylmethyl)-1H-indole-2,3-dione (2b) and 1-(naphthalen-2-ylmethyl)-1H-indole-2,3-dione (2c) exhibited nontoxic antiviral effects (EC50=6.8–12.0 µM) against vesicular stomatitis virus (VSV) and respiratory syncytial virus (RSV). To examine the contribution of the naphthalene ring, 1-methyl or 1-ethyl substituted compounds (2g-i) were also evaluated for in vitro antiviral activity, but these derivatives showed no antiviral activity against any of the viruses tested.