The synthesis and antibacterial activity evaluation of oxazolidinone-deferasirox conjugates  

噁唑烷酮-地拉罗司偶联物的合成及抗菌活性评价

作　　者：Xintong Zhao Yuhua Hu Tong Qin Tianlei Li Wenxuan Zhang Song Wu 赵欣彤;胡宇华;秦通;李天磊;张文轩;吴松(中国医学科学院&北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050)

机构地区：[1]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

出　　处：《Journal of Chinese Pharmaceutical Sciences》2022年第12期946-952,共7页中国药学（英文版）

基　　金：The CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-1-028).

摘　　要：We reported herein the synthesis and antibacterial activity evaluation of two oxazolidinone-deferasirox conjugates with different linkers that were designed based on the“Trojan horse”strategy.The conjugates could combine with Fe^(3+)ions as the deferasirox.However,both conjugates were inactive against tested bacteria,including S.aureus,E.coli,A.baumannii,and P.aeruginosa.The results suggested that the synthesized iron chelator deferasirox was not suitable as a siderophore of the bacteria to transport the antibiotic,or the coupling linker of the synthesized conjugates could not be hydrolyzed to release the oxazolidinone in the cytoplasm.Therefore,the design and synthesis of oxazolidinone-deferasirox conjugates need further exploration.本文基于“特洛伊木马”策略设计合成了两种具有不同连接臂的噁唑烷酮-地拉罗司偶联物,并进行了抗菌活性评价。与地拉罗司相同,两种偶联物均可与Fe^(3+)结合。然而,其对所测试的菌株(包括金黄色葡萄球菌、大肠杆菌、鲍曼不动杆菌和铜绿假单胞菌)均无活性。结果表明,合成的铁螯合剂地拉罗司可能不适合作为细菌转运抗生素的铁离子载体,或者合成的偶联物的连接臂不能在细菌细胞质中水解释放噁唑烷酮,噁唑烷酮-地拉罗司偶联物的设计与合成还需要进一步探索。

关 键 词：OXAZOLIDINONE DEFERASIROX ANTIBACTERIAL SIDEROPHORE “Trojan horse”strategy 

分 类 号：R917[医药卫生—药物分析学]