Identification of Terfenadine as an Inhibitor of HumanCD81-Receptor HCV-E2 Interaction: Synthesis and Structure Optimization

Terfenadine (4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-(4-tert-butyl-phenyl)-butan-1-ol) was identified in a biological screening to be a moderate inhibitor (27 % inhibition) of the CD81-LEL–HCV-E2 interaction. To increase the observed biological activity, 63 terfenadine derivates were synthesized...

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Detalles Bibliográficos
Autores principales: Holzer, Marcel, Ziegler, Sigrid, Albrecht, Beatrice, Kronenberger, Bernd, Kaul, Artur, Bartenschlager, Ralf, Kattner, Lars, Klein, Christian D., Hartmann, Rolf W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2008
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245452/
https://www.ncbi.nlm.nih.gov/pubmed/18560330
http://dx.doi.org/10.3390/molecules13051081
Descripción
Sumario:Terfenadine (4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-(4-tert-butyl-phenyl)-butan-1-ol) was identified in a biological screening to be a moderate inhibitor (27 % inhibition) of the CD81-LEL–HCV-E2 interaction. To increase the observed biological activity, 63 terfenadine derivates were synthesized via microwave assisted nucleophilic substitution. The prepared compounds were tested for their inhibitory potency by means of a fluorescence labeled antibody assay using HUH7.5 cells. Distinct structure-activity relationships could be derived. Optimization was successful, leading to 3g, identfied as the most potent compound (69 % inhibition). Experiments with viral particles revealed that there might be additional HCV infection reducing mechanisms.

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