2. Academic Validation
  3. Synthesis and evaluation of novel pleuromutilin derivatives targeting the 50S ribosomal subunit for antibacterial ability

Synthesis and evaluation of novel pleuromutilin derivatives targeting the 50S ribosomal subunit for antibacterial ability

  • Eur J Med Chem. 2023 Oct 20:262:115882. doi: 10.1016/j.ejmech.2023.115882.
Qinqin Liu 1,  Hongjuan Zhang 2,  YunPeng Yi 3,  Panpan Wang 2,  Wanxia Pu 2,  Shengyi Wang 2,  Ruofeng Shang 4
Affiliations

Affiliations

  • 1 Key Laboratory of New Animal Drug Project, Gansu Province/Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs/Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, 730050, China. Electronic address: l18736127157@163.com.
  • 2 Key Laboratory of New Animal Drug Project, Gansu Province/Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs/Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, 730050, China.
  • 3 Shandong Provincial Animal and Poultry Green Health Products Creation Engineering Laboratory, Institute of Poultry Science, Shandong Academy of Agricultural Science, 202 Gongyebeilu, Jinan, 250023, Shandong, China.
  • 4 Key Laboratory of New Animal Drug Project, Gansu Province/Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs/Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, 730050, China. Electronic address: shangrf1974@163.com.
PMID: 37879170 DOI: 10.1016/j.ejmech.2023.115882
Abstract

Multidrug-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus, have become a major global public health concern. Therefore, developing new Antibiotics that do not possess cross-resistance for the currently available Antibiotics is critical. Herein, we synthesized a novel class of pleuromutilin derivatives containing substituted triazine with improved Antibacterial activity. Among these derivatives, 6d, which contains 4-dimethylamino-1,3,5-triazine in the side chain of pleuromutilin, exhibited highly promising antimicrobial activity and mitigated Antibiotic resistance. The high Antibacterial potency of 6d was further supported by docking model analysis and green fluorescent protein inhibition assay. Additionally, cytotoxicity and acute oral toxicity evaluation and in vivo mouse systemic Infection experiments revealed that 6d possessed tolerable toxicity and promising therapeutic efficacy.

Keywords

Antibacterial activity; Pleuromutilin derivatives; Synthesis; Toxicity.

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