Complexation of a 1-indanone thiosemicarbazone with hydroxypropyl-b-cyclodextrin enhances its activity against a hepatitis C virus surrogate model

GLISONI, R.J., CASTRO, E.F, CAVALLARO, L.V. MOGLIONI, A.G., SOSNIK, A.

JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY

AMER SCIENTIFIC PUBLISHERS

Año: 2015 vol. 15 p. 4224 - 4228

1533-4880

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.