title: Complexation of a 1-Indanone Thiosemicarbazone with Hydroxypropyl-β-Cyclodextrin Enhances Its Activity Against a Hepatitis C Virus Surrogate Model.
abstract: The current standard of care of the infection by hepatitis C virus (HCV) is effective in a limited number of patients and the high cost hinders therapy affordability and compliance. In this context, the research of new direct-acting antiviral agents (DAAs) for a more effective and long-lasting therapy is an urgent need and an area of active investigation. In an effort to develop novel DAAs, a series of 1-indanone thiosemicarbazones (TSCs) was synthesized and fully characterized. However, the high self-aggregation tendency and extremely poor aqueous solubility of these antiviral candidates often preclude their reliable biological evaluation in vitro. To maintain constant TSC concentrations over the biological assays, different TSC/cyclodextrin complexes were produced. In the present work, we report for the first time the cytotoxicity and antiviral activity of 5,6-dimethoxy TSC inclusion complexes with hydroxypropyl-β-cyclodextrin on bovine viral diarrhea virus (BVDV) as HCV surrogate model. Results showed a potent suppression of the virus replication, with greater activity for the inclusion complexes than the free compound.
authors.forename: Romina J
authors.initials: RJ
authors.lastname: Glisoni
authors.forename: Eliana F
authors.initials: EF
authors.lastname: Castro
authors.forename: Lucía V
authors.initials: LV
authors.lastname: Cavallaro
authors.forename: Albertina G
authors.initials: AG
authors.lastname: Moglioni
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sosnik
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects*; D016174:Hepacivirus; D006801:Humans; D007189:Indans / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D008954:Models, Biological; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000998:Antiviral Agents; D007189:Indans; D013882:Thiosemicarbazones; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C013352:indacrinone