We have prepared a new class of chalcones characterized by strong cytotoxic activity. Looking for other possible application of the compounds, preliminary tests of antiviral activity of selected derivatives were performed. Six randomly selected compounds was screened against classical swine fever virus (CSFV) which is the causative agent of a highly contagious, economically damaging disease of swine and wild boars.

The inhibition of the in vitro propagation of CSFV by tested compounds was evaluated following a procedure reported previously [1]. In brief, Swine kidney cells (SK6) were infected with CSFV and incubated with each compound at various concentrations from 0.1 - 3 µg/ml for up to 3 days. Due to the lack of cytopathic effect caused by CSFV, accurate virus propagation measurement was based on the visualization of the foci caused by CSFV (pseudoplaques) using immunoperoxidase monolayer assay (IPMA) which detects the areas of maximum concentration of glycoproteins of the viral outer layer. The effective doses for 50% virus reduction (IC₅₀) and cytotoxic concentrations at 50% cell death (CC₅₀) of the above compounds determined in CellTiter 96 AQ_ueous non-radioactive cell proliferation assay (MTS) are summarized in the Table. Both CC₅₀ and IC₅₀ values were used to calculate the in vitro selectivity index (CC₅₀/IC₅₀).

^a Compound concentration required to reduce cell viability by 50%.

^b Compound concentration required to reduce virus plaque formation by 50%.

^c  In vitro selectivity index (CC50/IC50).

 ND: not determined.

 NA: not available.

The results of the preliminary studies demonstrated that all tested compounds exhibited antiviral properties against CSFV in a dose-dependent manner evidenced by the reduction in the number and size of pseudoplaques, suggesting that the drugs inhibited proliferation and spread of the virus. Among the tested compounds, AMG-164 showed the most potent inhibitory activity on CSFV with an IC₅₀ value of approximately 0.18 mg/ml. All the other compounds displayed a lower inhibitory potency, with IC₅₀ values ranging from 0.26 mg/ml for AMG-161 to 1.8 mg/ml for AMG-170. The difference in antiviral activity of tested compounds could be due to the differences in cellular uptake and intracellular distribution.

References

1. Krol E., Wandzik I., Szeja W., Grynkiewicz G., Szewczyk B. Antiviral Res.   2010   86, 154-162; In vitro antiviral activity of some uridine derivatives of 2-deoxy sugars against classical swine fever virus.

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