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Novel natural osthole-inspired amphiphiles as membrane targeting antibacterials against methicillin-resistant Staphylococcus aureus (MRSA).
Yang, Ruige; Xue, Zihan; Li, Xinhui; Xu, Ting; Zhong, Yan; Hu, Songlin; Qin, Shangshang; Guo, Yong.
Afiliação
  • Yang R; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan Province, China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province,
  • Xue Z; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
  • Li X; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
  • Xu T; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan Province, China.
  • Zhong Y; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan Province, China.
  • Hu S; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan Province, China.
  • Qin S; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
  • Guo Y; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan Province, China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province,
Eur J Med Chem ; 271: 116449, 2024 May 05.
Article em En | MEDLINE | ID: mdl-38691893
ABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) is a widespread pathogen causing clinical infections and is multi-resistant to many antibiotics, making it urgent need to develop novel antibacterials to combat MRSA. Herein, we designed and prepared a series of novel osthole amphiphiles 6a-6ad by mimicking the structures and function of antimicrobial peptides (AMPs). Antibacterial assays showed that osthole amphiphile 6aa strongly inhibited S. aureus and 10 clinical MRSA isolates with MIC values of 1-2 µg/mL, comparable to that of the commercial antibiotic vancomycin. Additionally, 6aa had the advantages of rapid bacteria killing without readily developing drug resistance, low toxicity, good membrane selectivity, and good plasma stability. Mechanistic studies indicated that 6aa possesses good membrane-targeting ability to bind to phosphatidylglycerol (PG) on the bacterial cell membranes, thereby disrupting the cell membranes and causing an increase in intracellular ROS as well as leakage of proteins and DNA, and accelerating bacterial death. Notably, in vivo activity results revealed that 6aa exhibits strong anti-MRSA efficacy than vancomycin as well as a substantial reduction in MRSA-induced proinflammatory cytokines, including TNF-α and IL-6. Given the impressive in vitro and in vivo anti-MRSA efficacy of 6aa, which makes it a potential candidate against MRSA infections.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Testes de Sensibilidade Microbiana / Cumarínicos / Staphylococcus aureus Resistente à Meticilina / Antibacterianos Limite: Animals / Humans Idioma: En Revista: Eur J Med Chem Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Testes de Sensibilidade Microbiana / Cumarínicos / Staphylococcus aureus Resistente à Meticilina / Antibacterianos Limite: Animals / Humans Idioma: En Revista: Eur J Med Chem Ano de publicação: 2024 Tipo de documento: Article