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Synthesis and Anti-BVDV Activity of Acridones As New Potential Antiviral Agents 1

Abstract : 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.
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https://hal.archives-ouvertes.fr/hal-02459231
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Submitted on : Wednesday, January 29, 2020 - 11:45:15 AM
Last modification on : Tuesday, October 19, 2021 - 10:59:50 PM

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Oriana Tabarrini, Giuseppe Manfroni, Arnaldo Fravolini, Violetta Cecchetti, Stefano Sabatini, et al.. Synthesis and Anti-BVDV Activity of Acridones As New Potential Antiviral Agents 1. Journal of Medicinal Chemistry, American Chemical Society, 2006, 49 (8), pp.2621-2627. ⟨10.1021/jm051250z⟩. ⟨hal-02459231⟩

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