摘要
目的:设计合成新型氟喹诺酮C-3位异羟肟酸类衍生物并初筛其体外抗菌活性。方法:利用电子等排体及金属螯合作用,用异羟肟酸或含L-苏氨酸的异羟肟酸片段替代氟喹C-3位羧酸,制备了一系列氟喹诺酮类衍生物。结果:共设计合成14个氟喹诺酮异羟肟酸类衍生物,结构经1H NMR和HR-MS确证,并进行体外抗菌活性测定。结论:体外抗菌活性显示部分化合物对革兰阳性菌、阴性菌表现出中等的抗菌活性(MIC:0. 5～8μg·mL^(-1)),弱于阳性对照左氧氟沙星。其中针对所选的金黄色葡萄球菌和大部分革兰阴性菌,化合物19和34表现出较好的抗菌活性(MIC:0. 12～4μg·mL^(-1))。
Objective: To design and synthesize a series of fluoroquinolones C-3 hydroxamic acid derivatives and evaluate their in vitro antibacterial effects. Methods: A series of fluoroquinolone derivatives were synthesized by using isostere and metal ion chelation to replace fluoroquinoline C-3 carboxylic acid with hydroxamic acid or L-threonine-containing hydroxamic acid moiety. Results: Fourteen novel compounds were synthesized and characterized by 1H NMR and HRMS and tested for their antibacteria activity in vitro. Conclusion: In vitro antibacterial activity showed that some compounds showed moderate antibacterial activity against Gram-positive and negative bacteria (MIC:0.5-8 μg·mL ^-1), weaker than levofloxacin. Among them , for the selected Staphylococcus aureus and most Gram-negative bacteria, the compounds 19, 34 exhibited better antibacterial activity ( MIC:0.12 ~ 4 μg·mL^-1).
作者
邵端阳
王明华
张国宁
王菊仙
游学甫
李东辉
王玉成
SHAO Duan-yang;WANG Ming-hua;ZHANG Guo-ning;WANG Ju-xian;YOU Xue-fu;LI Dong-hui;WANG Yu-cheng(College of Pharmacy , Jinzhou Medical University, Jinzhou 121001 ,China;Institute of Medical Biotechnology,Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2019年第6期732-738,共7页
Chinese Journal of New Drugs
基金
国家自然科学基金资助项目(81703366)
中国医学科学院医学与健康科技创新工程经费资助项目(2016-I2M-3-014)
关键词
氟喹诺酮
异羟肟酸
抗菌活性
合成
fluoroquinolones
hydroxamic acid
antibacterial activity
synthesis
