摘要
目的双键化多黏菌素B1的制备、结构分析及对其抗菌活性进行初步研究。方法采用制备色谱对硫酸多黏菌素B中的双键化组分纯化后通过高效液相色谱-四级杆飞行质谱及核磁技术确证其结构。测定双键化组分对三种革兰阴性菌包括鲍曼不动杆菌、铜绿假单胞菌、肺炎克雷伯菌的最低抑菌浓度,与多黏菌素B1进行比较,评价其抑菌效果。结果高分辨质谱及核磁数据证明双键化组分的N-端酰基链为反式-6-甲基辛2-烯酰基,命名该组分为2’,3’-脱氢多黏菌素B1。根据最低抑菌浓度,该组分对三种革兰阴性菌的抑菌活性与多黏菌素B1相当或者较好。结论本研究确证了2’,3’-脱氢多黏菌素B1的结构并证明该组分具有较好的抑菌活性,为多黏菌素B质量标准的完善和筛选高活性多黏菌素提供了研究基础。
Objective A preparation and structural analysis method was established for the vinyl polymyxin B1.The antibacterial activity of the new component was also studied.Methods The vinyl polymyxin B1 was purified by preparative chromatography,and its structure was analyzed by HPLC-Q/TOF-MS and NMR.The antibacterial effect of vinyl polymyxin B1 and polymyxin B1 were evaluated by minimum inhibitory concentrations (MIC) of three Gram-negative bacteria,including Acinetobacter baumannii,Pseudomonas aeruginosa and Klebsiella pneumoniae.Results The N-terminal fatty acyl of the vinyl polymyxin B1 was confirmed to be trans-6-methyloct-2-enoyl by high resolution mass spectrometry and nuclear magnetic resonance (NMR).The component was named as 2’,3’-dehydro Polymyxin B1 (2’,3’-dehydro PMB1).According to the MICs,2’,3’-dehydro PMB1 exhibited antimicrobial activity equal or better than PMB1.Conclusion This study confirmed the structure of 2’,3’-dehydro PMB1 and proved that the component had good antibacterial activity.It also provided the research basis for the improvement of the quality standard of polymyxin B and the screening of high activity polymyxin.
作者
张含智
孙宁
刘笑芬
秦峰
罗文燕
黄臻辉
卞星晨
丁金国
刘浩
Zhang Han-zhi;Sun Ning;Liu Xiao-fen;Qin Feng;Luo Wen-yan;Huang Zhen-hui;Bian Xing-chen;Ding Jin-guo;Liu Hao(Shanghai Institute for Food and Drug Control,Shanghai 201203;Shanghai Institute of Advanced Immunochemical Studies,ShanghaiTech University,Shanghai 201203;Institute of Antibiotics,Huashan Hospital Affiliated to Fudan University,Shanghai 200040;Department of Chemistry and Institutes of Biomedical Sciences,Fudan University,Shanghai 200438;SPH No.1 Biochemical and Pharmaceutical Co.,LTD,Shanghai 200240)
出处
《国外医药（抗生素分册）》
CAS
2020年第6期475-481,共7页
World Notes on Antibiotics
基金
上海市科学技术委员会科研计划项目(17DZ1910400)
上海市科委项目编号:20142202200
上海市药品监督管理局课题(YB-2020-04)。
