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Design, synthesis, and biological evaluation of novel polymyxin B analogues
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A-long CUI, Xin-xin HU, Yan GAO, Jie JIN, Hong YI, Yang CHEN, Qi-yang HE, Xue-fu YOU, Zhuo-rong LI*
Acta Pharmaceutica Sinica | 2019, 54(11) : 2031 - 2038
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Acta Pharmaceutica Sinica | 2019, 54(11): 2031-2038
• Special Reports •
Design, synthesis, and biological evaluation of novel polymyxin B analogues
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A-long CUI, Xin-xin HU, Yan GAO, Jie JIN, Hong YI, Yang CHEN, Qi-yang HE, Xue-fu YOU, Zhuo-rong LI*
Affiliations
  • Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Published: 2019-11-12 doi: 10.16438/j.0513-4870.2019-0500
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Polymyxin B and polymyxin E (colistin) are increasingly used as last-resort drugs for treatment of infections caused by multidrug-resistant gram-negative pathogens. Unfortunately, the application was limited due to the serious side effects, especially nephrotoxicity. Very recently, the need for developing more tolerated and more effective polymyxin analogues has grown. This study details the design, synthesis, and evaluation of two classes of polymyxin B analogues with varying hydrophobicity and bulkiness at the N-terminal fatty acyl chain or position 6 amino acid. 20 polymyxin B analogues were synthesized and the chemical structures of the analogues were confirmed by HR-MS and 1H NMR spectra. Compounds 7e (MIC:0.5-4 μg·mL-1) and 7l (MIC:0.25-2 μg·mL-1) showed similar or better antimicrobial activity against both susceptible and resistant strains of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa compared to polymyxin B (MIC:0.5-2 μg·mL-1). Besides, compound 7l (CC50:217.1±13.2 μg·mL-1) displayed noticeably decreased renal cytotoxicity compared to polymyxin B (CC50:120.3±6.0 μg·mL-1). This work establishes the base of further study on the structure-activity relationship of polymyxin B.

gram-negative pathogens  /  polymyxin B  /  novel analogues  /  antimicrobial activity  /  nephrotoxicity
A-long CUI, Xin-xin HU, Yan GAO, Jie JIN, Hong YI, Yang CHEN, Qi-yang HE, Xue-fu YOU, Zhuo-rong LI. Design, synthesis, and biological evaluation of novel polymyxin B analogues[J]. Acta Pharmaceutica Sinica, 2019 , 54 (11) : 2031 -2038 . DOI: 10.16438/j.0513-4870.2019-0500
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Article Info
doi: 10.16438/j.0513-4870.2019-0500
  • Receive Date：2019-06-21
  • Online Date：2026-01-26
  • Published：2019-11-12
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  • Received：2019-06-21
  • Revised：2019-07-24
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    Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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