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Synthesis and antibacterial activities of heterocyclic ring-fused 20(S)-protopanaxadiol derivatives.

Author information

Affiliations

  • 1. Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
      Authors
    • Zhang DJ 1
    • Yue YX 1
    • Qiu WW 1
    (3 authors)
  • 2. State Key Laboratory of Drug Research, Centre for Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
      Authors
    • Yuan ZQ 2
    (1 author)
  • 3. Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China.
      Authors
    • Zhang M 3
    • Wu WJ 3
    (2 authors)
  • 4. State Key Laboratory of Drug Research, Centre for Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China.
      Authors
    • Yang CG 4
    (1 author)

Bioorganic & Medicinal Chemistry, 30 Aug 2024, 112:117901
https://doi.org/10.1016/j.bmc.2024.117901 PMID: 39232465 

Abstract 

Multidrug-resistant (MDR) bacterial infections are becoming a life-threatening issue in public health; therefore, it is urgent to develop novel antibacterial agents for treating infections caused by MDR bacteria. The 20(S)-protopanaxadiol (PPD) derivative 9 was identified as a novel antibacterial hit compound in screening of our small synthetic natural product-like (NPL) library. A series of novel PPD derivatives with heterocyclic rings fused at the C-2 and C-3 positions of the A-ring were synthesized and their antibacterial activities against Staphylococcus aureus (S. aureus) Newman strain and MDR S. aureus strains (USA300, NRS-1, NRS-70, NRS-100, NRS-108, NRS-271, XJ017, and XJ036) were evaluated. Among these compounds, quinoxaline derivative 56 (SH617) exhibited the highest activity with MICs of 0.5-4 μg/mL against the S. aureus Newman strain and the eight MDR S. aureus strains. Its antibacterial activity was comparable to that of the positive control, vancomycin. In the zebrafish, 56 revealed no obvious toxicity even at a high administered dose. In vivo, following a lethal infection induced by USA300 strains in zebrafish, 56 exhibited significantly increased survival rates in a dose-dependent manner.

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Read article at publisher's site: https://doi.org/10.1016/j.bmc.2024.117901

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Funding 

Funders who supported this work.

National Natural Science Foundation of China (3)