title: Synthesis and anti-BVDV activity of acridones as new potential antiviral agents.
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.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia, Via del Liceo 1, 06123 Perugia, Italy. oriana.t@unipg.it
authors.forename: Oriana
authors.initials: O
authors.lastname: Tabarrini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Manfroni
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Fravolini
authors.forename: Violetta
authors.initials: V
authors.lastname: Cecchetti
authors.forename: Stefano
authors.initials: S
authors.lastname: Sabatini
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jef
authors.initials: J
authors.lastname: Rozenski
authors.forename: Bruno
authors.initials: B
authors.lastname: Canard
authors.forename: Hélène
authors.initials: H
authors.lastname: Dutartre
authors.forename: Jan
authors.initials: J
authors.lastname: Paeshuyse
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054831:Acridones; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects*; D015195:Drug Design; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000166:Acridines; D054831:Acridones; D000998:Antiviral Agents; C041300:acridone