Novel partially reversible NDM-1 inhibitors based on the naturally occurring houttuynin.
Bioorg Chem
; 147: 107328, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38583248
ABSTRACT
Discovering novel NDM-1 inhibitors is an urgent task for treatment of 'superbug' infectious diseases. In this study, we found that naturally occurring houttuynin and its sulfonate derivatives might be effective NDM-1 inhibitors with novel mechanism, i.e. the attribute of partially covalent inhibition of sulfonate derivatives of houttuynin against NDM-1. Primary structure-activity relationship study showed that both the long aliphatic side chain and the warhead of aldehyde group are vital for the efficiency against NDM-1. The homologs with longer chains (SNH-2 to SNH-5) displayed stronger inhibitory activities with IC50 range of 1.1-1.5 µM, while the shorter chain the weaker inhibition. Further synergistic experiments in cell level confirmed that all these 4 compounds (at 32 µg/mL) recovered the antibacterial activity of meropenem (MER) against E. coli BL21/pET15b-blaNDM-1.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Testes de Sensibilidade Microbiana
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Relação Dose-Resposta a Droga
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Escherichia coli
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Antibacterianos
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article