INVESTIGADORES
MATHET Veronica Lidia
congresos y reuniones científicas
Título:
Novel 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β-cyclodextrin are effective antivirals against the hepatitis C virus (HCV).
Autor/es:
ROMINA J. GLISONIA; .; MARÍA L. CUESTAS; ; VERÓNICA L. MATHET, ; JOSÉ R. OUBIÑA, ; ALBERTINA G. MOGLIONI ; ALEJANDRO SOSNI
Lugar:
Natal
Reunión:
Congreso; COLAOB-Congreso Latinoamericano de Biomateriales, Órganos artificiales e Ingeniería de tejidos; 2012
Resumen:
The hepatitis C virus (HCV)
is a major cause of acute and chronic hepatitis in humans. Approximately 5% of
the infected people die from cirrhosis or hepatocellular carcinoma. The current
gold-standard therapy comprises a combination of pegylated-interferon and
ribavirin. Due to the relatively low effectiveness, the prohibitive costs and
the extensive side effects of the treatment, an intense research for new
anti-HCV agents is taking place. Thiosemicarbazones (TSCs) have shown antiviral
activity against a wide range of DNA and RNA viruses. However, their extremely
low aqueous solubility and high self-aggregation tendency often preclude their
reliable biological evaluation
in vitro1. In this work, we investigated and compared for
the first time the anti- HCV activity of two novel 1-indanone TSCs,
5,6-dimethoxy-1-indanone TSC and 5,6-dimethoxy-1-indanone N4-allyl TSC, and
their inclusion complexes with
hydroxypropyl-β-CD (HP-b-CD)2
in Huh7.5 cells containing the full-length and the subgenomic subgenotype 1b
HCV replicon system. Studies of physical stability in culture medium showed
that free TSCs precipitated rapidly and formed submicron aggregates.
Conversely, TSC complexation with HP-b-CD led to were more stable
systems with minimal size growth and concentration loss due to drug
precipitation2. More importantly, both TSCs and their inclusion complexes
displayed a potent suppression of the HCV replication in both cell lines with
no cytotoxic effects. The mechanism would involve the inhibition of non-structural
proteins of the virus. In addition, findings suggested that the cyclodextrin
released the drug to the culture medium over time. This platform could be
exploited for the development of TSC formulations and delivery systems with
improved features towards the evaluation of the drug pharmacokinetics in animal
models.