Novel pyridinium-type fullerene derivatives as multitargeting inhibitors of HIV-1 reverse transcriptase, HIV-1 protease, and HCV NS5B polymerase.
Bioorg Med Chem Lett
; 49: 128267, 2021 10 01.
Article
em En
| MEDLINE
| ID: mdl-34271071
ABSTRACT
In the present study, we newly synthesized four types of novel fullerene derivatives pyridinium/ethyl ester-type derivatives 3b-3l, pyridinium/carboxylic acid-type derivatives 4a, 4e, 4f, pyridinium/amide-type derivative 5a, and pyridinium/2-morpholinone-type derivative 6a. Among the assessed compounds, cis-3c, cis-3d, trans-3e, trans-3h, cis-3l, cis-4e, cis-4f, trans-4f, and cis-5a were found to inhibit HIV-1 reverse transcriptase (HIV-RT), HIV-1 protease (HIV-PR), and HCV NS5B polymerase (HCV NS5B), with IC50 values observed in the micromolar range. Cellular uptake of pyridinium/ethyl ester-type derivatives was higher than that of corresponding pyridinium/carboxylic acid-type derivatives and pyridinium/amide-type derivatives. This result might indicate that pyridinium/ethyl ester-type derivatives are expected to be lead compounds for multitargeting drugs to treat HIV/HCV coinfection.
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MEDLINE
Assunto principal:
Compostos de Piridínio
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Proteínas não Estruturais Virais
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Inibidores da Protease de HIV
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Inibidores da Transcriptase Reversa
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Fármacos Anti-HIV
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Fulerenos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article