Synthesis and biological evaluation of berberine derivatives as a new class of broad-spectrum antiviral agents against Coxsackievirus B.
Bioorg Chem
; 95: 103490, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31855821
ABSTRACT
A series of novel berberine (BBR) analogues were prepared and tested for their antiviral potencies against six different genotype Coxsackievirus B (CVB1-6) strains, taking BBR core for structural modification. Structure-activity relationship (SAR) research revealed that introduction of a primary amine through a linker at position 3 might be beneficial for both antiviral activity and safety. Compound 14c displayed most promising inhibitory potency with IC50 values of 3.08-9.94 µM against tested CVBs 2-6 strains and satisfactory SI value of 34.3 on CVB3, better than that of BBR. Also, 14c could inhibit CVB3 replication through down-regulating the expression of VP1 protein and VP1 RNA. The mechanism revealed that 14c could suppress host components JNK-MAPK, ERK-MAPK and p38-MAPK activation. Therefore, BBR derivatives were considered to be a new class of anti-CVB agents with an advantage of broad-spectrum anti-CVB potency.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Berberina
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Enterovirus Humano B
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article