2. Academic Validation
  3. Design, synthesis, and antibacterial evaluation of PFK-158 derivatives as potent agents against drug-resistant bacteria

Design, synthesis, and antibacterial evaluation of PFK-158 derivatives as potent agents against drug-resistant bacteria

  • Bioorg Med Chem Lett. 2021 Jun 1:41:127980. doi: 10.1016/j.bmcl.2021.127980.
Wei Wang 1,  You-Wen Zhang 2,  Shang-Jiu Hu 2,  Wei-Ping Niu 2,  Guo-Ning Zhang 2,  Mei Zhu 2,  Ming-Hua Wang 2,  Fan Zhang 3,  Xue-Mei Li 4,  Ju-Xian Wang 5
Affiliations

Affiliations

  • 1 School of Pharmacy, Jinzhou Medical University, Jinzhou 121001, PR China.
  • 2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
  • 3 School of Pharmacy, Jinzhou Medical University, Jinzhou 121001, PR China. Electronic address: [email protected].
  • 4 Center for Drug Evaluation, National Medical Products Administration, Beijing 100022, PR China. Electronic address: [email protected].
  • 5 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China. Electronic address: [email protected].
PMID: 33766773 DOI: 10.1016/j.bmcl.2021.127980
Abstract

Infections caused by Antibiotic resistant bacteria are a major health concern throughout the world. It is well known that PFK-158 can enhance the Antibacterial effect of polymyxin, but its own anti-bactericidal effect is rarely discussed. In order to investigate the anti-bactericidal effect of PFK-158 and its derivatives, PFK-158 and 35 derivatives were designed, synthesized, and evaluated for their Antibacterial activities. Compounds A1, A3, A14, A15 and B6 exhibited potent Antibacterial effect against both clinical drug sensitive and resistant Gram-positive bacteria, and they are 2-8 folds more potent than levofloxacin against Methicillin-resistant staphylococcus epidermidis (MRSE). A significant synergistic effect of these compounds and polymyxin against drug-resistant Gram-negative bacteria, which is similar to PFK-158 was also observed. The result can provided a new and broader prospect for the development of new medicine against drug-resistant bacteria.

Keywords

Antibacterial effect; Drug-resistant bacteria; PFK-158 derivatives; Synthesized.

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