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  3. Design, synthesis and antibacterial evaluation of pleuromutilin derivatives

Design, synthesis and antibacterial evaluation of pleuromutilin derivatives

  • Bioorg Med Chem. 2022 Apr 1;59:116676. doi: 10.1016/j.bmc.2022.116676.
Guangxu Wu 1,  Zihao Zhu 2,  Jishun Li 2,  Xinyu Luo 2,  Wenyong Zhu 3,  Guoyang Liao 3,  Jie Xia 2,  Wenxuan Zhang 2,  Weidong Pan 4,  Tianlei Li 5,  Song Wu 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
  • 2 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
  • 3 Institute of Medical Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Kunming 650031, Chin.
  • 4 State Key Laboratory of Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China.
  • 5 State Key Laboratory of Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China. Electronic address: [email protected].
PMID: 35220163 DOI: 10.1016/j.bmc.2022.116676
Abstract

We report herein the design, synthesis, and structure-activity relationship studies of pleuromutilin derivatives containing urea/thiourea functionalities. The Antibacterial activities of these new pleuromutilin derivatives were evaluated in vitro against Gram-positive pathogens (GPPs) (Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium) and Mycoplasma pneumoniae by the broth dilution method. Most of the targeted compounds exhibit good potency in inhibiting the growth of pathogens including Methicillin-susceptible S. aureus (MSSA, ATCC29213, MIC: 0.0625-16 μg/mL), Methicillin-resistant S. aureus (MRSA, ATCC43300, MIC: 0.125-16 μg/mL) and M. pneumoniae (ATCC15531 MIC: 0.125-1 μg/mL, ATCC29342 MIC: 0.0625-0.25 μg/mL and drug resistant strain MIC: 0.5-2 μg/mL). In particular, the compounds 6m and 6n containing phenyl-urea group showed excellent activity with the MIC value less than 0.0625 μg/mL against S. aureus ATCC29213. The compound 6h exhibited better activity than tiamulin against Methicillin-resistant S. aureus ATCC43300.

Keywords

Antibacterial agents; Design and synthesis; Gram-positive pathogens; New pleuromutilin derivatives; Structure-activity relationship; Urea/thiourea functionalities.

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