Discovery of Novel Pleuromutilin Derivatives as Potent Antibacterial Agents for the Treatment of MRSA Infection.
Molecules
; 27(3)2022 Jan 29.
Article
em En
| MEDLINE
| ID: mdl-35164203
ABSTRACT
A series of novel pleuromutilin derivatives containing nitrogen groups on the side chain of C14 were synthesized under mild conditions. Most of the synthesized derivatives displayed potent antibacterial activities. Compound 9 was found to be the most active antibacterial derivative against MRSA (MIC = 0.06 µg/mL). Furthermore, the result of time-kill curves showed that compound 9 had a certain inhibitory effect against MRSA in vitro. Moreover, according to a surface plasmon resonance (SPR) study, compound 9 (KD = 1.77 × 10-8 M) showed stronger affinity to the 50S ribosome than tiamulin (KD = 2.50 × 10-8 M). The antibacterial activity of compound 9 was further evaluated in an MRSA-infected murine thigh model. Compared to the negative control group, tiamulin reduced MRSA load (~0.7 log10 CFU/mL), and compound 9 performed a treatment effect (~1.3 log10 CFU/mL). In addition, compound 9 was evaluated in CYP450 inhibition assay and showed only moderate in vitro CYP3A4 inhibition (IC50 = 2.92 µg/mL).
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos Policíclicos
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Infecções Estafilocócicas
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Diterpenos
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Staphylococcus aureus Resistente à Meticilina
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Descoberta de Drogas
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Antibacterianos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Molecules
Assunto da revista:
BIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China