Inhibition of herpes simplex virus type 1 and adenovirus type 5 by heterocyclic Schiff bases of aminohydroxyguanidine tosylate

Das, Arima; Trousdale, Melvin D; Ren, Shijun; Lien, Eric J

Eleven heterocyclic Schiff bases of aminohydroxyguanidine tosylate (SB-AHGs), compounds I–XI, were tested for antiviral activity against herpes simplex virus type 1 (HSV-1) and adenovirus type 5 (Ad 5) via plaque reduction and virus yield reduction assays. This work was undertaken to test the hypothesis that low molecular weight SB-AHGs (MW<235 for the free SB) make better antiviral agents than high MW SB-AHGs (MW>300). The plaque reduction assay method demonstrated that three compounds, I, VII and IX, had moderate activity against HSV-1, with 50% inhibitory concentration (IC(50)) values of 38.0, 23.5 and 52.1 μM, respectively. Against Ad 5, compounds I, VIII and XI exhibited moderate activity, with IC(50) values of 52.7, 19.3 and 5.1 μM, respectively. Among the compounds screened, compound I (1-[(3′-hydroxy-6′-methyl-2′-pyridyl)methylene]amino-3-hydroxyguanidine tosylate) was the most promising antiviral candidate, with selectivity indices (SI) of 10.2 (HSV-1) and 7.6 (Ad 5), respectively. Virus yield reduction assays indicated that compound I had less antiviral potency against HSV-1 than against Ad 5. The antiviral effects of compound I at a high input virus multiplicity of infection (MOI>5) indicated that compound I had effective anti-adenoviral activity at 24 h post infection. This work demonstrated that some of SB-AHGs only have moderate antiviral activities against Ad 5 and HSV-1 viruses. In general, low MW SB-AHGs have low cytotoxicities to the host cells.