Synthesis of 10,10'-bis(trifluoromethyl) marinopyrrole A derivatives and evaluation of their antiviral activities in vitro.
Eur J Med Chem
; 238: 114436, 2022 Aug 05.
Article
em En
| MEDLINE
| ID: mdl-35598412
Flavivirus and enterovirus can emerge unexpectedly in human populations and cause a spectrum of potentially severe diseases or even death. Since effective vaccine is currently unavailable against most of these deadly viruses, antiviral chemical drugs remain in urgent need. To meet this unmet demand, we developed a series of 10,10'-bis(trifluoromethyl) marinopyrrole A derivates bearing various substituents at C5'-positions, which exhibited impressive in vitro activities against flaviviruses (ZIKV, DENV, YFV, JEV) and enteroviruses (EV71, CA6, CA16). The lead compound 10,10'-bis(trifluoromethyl) marinopyrrole A 3 was highly effective against enteroviruses EV71 and CA16 in cultured cells, but with low inhibitory activities against flavivirus. Elaborately modified from compound 3, compounds 32 and 33 with sulfhydryl aliphatic chains were found as promising ZIKV and DENV inhibitor; pyrazine-containing compound 19 is a potent broad-spectrum flavivirus inhibitor; thiophene compound 15 exhibited prominent selective inhibitory effect against JEV-SA14, YFV-17D, in addition to broad-spectrum enterovirus inhibitory effect. These results thus suggest that the 5'-sulfhydryl derivates of 10,10'-bis(trifluoromethyl) marinopyrrole A may be promising lead compounds for the development of novel anti-flavivirus and anti-enterovirus drugs.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Enterovirus
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Infecções por Enterovirus
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Flavivirus
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Zika virus
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Infecção por Zika virus
Limite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
França