Design, synthesis, and biological evaluation of N-arylpiperazine derivatives as interferon inducers.
Bioorg Med Chem Lett
; 30(24): 127613, 2020 12 15.
Article
em En
| MEDLINE
| ID: mdl-33075488
ABSTRACT
Type I Interferon (IFN) signaling plays an important role in the immune defense system against virus infection and in the innate immune response, thus IFNs are widely used as anti-viral agents and treatment for immune disorder or cancer. However, there is a growing demand for novel small-molecule IFN inducer due to tolerance, toxicity, or short duration of action following direct administration of IFNs. In this study, we assessed arylpiperazine (ARP) as a new core skeleton of IFN inducer. To investigate structure-activity relationship, we designed and synthesized a series of ARP analogues and evaluated the ability to stimulate IFN response in THP-1 human monocyte cells. Compound 5i was identified as a potent type I IFN inducer as it significantly increased cytokine secretion and increased expression of various IFN-stimulating genes which are representative biomarkers of type I IFN pathway. Our results suggested a beneficial therapeutic potential of 5i as an anti-viral agent.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Monócitos
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Indutores de Interferon
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Coréia do Sul