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Tabarrini, O. et al.

Tabarrini, Manfroni, Fravolini, Cecchetti, Sabatini, De Clercq, Rozenski, Canard, Dutartre, Paeshuyse, Neyts,

Synthesis and anti-BVDV activity of acridones as new potential antiviral agents.

In this study we report the design, synthesis, and activity against bovine viral diarrhea virus (BVDV) of a novel series of acridone derivatives. BVDV is responsible for major losses in cattle. The virus is also considered to be a valuable surrogate for the hepatitis C virus (HCV) in antiviral drug studies. Some of the synthesized acridones elicited selective anti-BVDV activity with EC(50) values ranging from 0.4 to 4 microg/mL and were not cytotoxic at concentrations that were 25- to 200-fold higher (CC(50) >100 microg/mL). It was proven that the most potent acridone derivative 10 was able to not only protect cells from virus-induced cytopathic effect but also reduce the production of infectious virus and extracellular viral RNA. Furthermore, compound 10, as well as a number of other analogues, inhibited HCV replication to some extent. However, there was no direct correlation between anti-BVDV and anti-HCV activity. Thus, the acridone scaffold, when appropriately functionalized, can yield compounds with selective activity against pestiviruses and related viruses such as the HCV.[1]

References

Synthesis and anti-BVDV activity of acridones as new potential antiviral agents. Tabarrini, O., Manfroni, G., Fravolini, A., Cecchetti, V., Sabatini, S., De Clercq, E., Rozenski, J., Canard, B., Dutartre, H., Paeshuyse, J., Neyts, J. J. Med. Chem. (2006) [Pubmed]

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