D-氨基葡萄糖氟喹诺酮衍生物的合成及其抗菌活性研究  

Synthesis and antibacterial activity of D-glucosaminefluoroquinolone derivatives

作　　者：谢文文 范莉 胡军华[2] 宋宇璐 谭天富 李佳 陈娜 杨大成 XIE Wen-wen;FAN Li;HU Jun-hua;SONG Yu-lu;TAN Tian-fu;LI Jia;CHEN Na;YANG Da-cheng(Key Laboratory of Applied Chemistry of Chongqing Municipality,School of Chemistry and Chemical Engineering,Southwest University,Chongqing 400715,China;Citrus Research Institute,Southwest University,Chongqing 400712,China)

机构地区：[1]西南大学化学化工学院,重庆市高校应用化学重点实验室,重庆400715 [2]西南大学柑桔研究所,重庆400712

出　　处：《药学学报》2023年第11期3389-3399,共11页Acta Pharmaceutica Sinica

基　　金：重庆市技术创新与应用发展专项面上项目(cstc2019jscx-msxmX0123);重庆市大学生创新创业训练计划项目(s202210635211);国家重大研发计划项目:溃疡病绿色高效防控技术体系集成创新与示范(2022YFD1400200)。

摘　　要：基于糖类药物的修饰或用糖类分子改造其他活性物质的思路,将具有多种活性的D-氨基葡萄糖与氟喹诺酮类(fluoroquinolones,FQs)进行拼合,设计并合成了16个D-氨基葡萄糖的FQs衍生物。抗人致病菌和抗柑橘溃疡病菌活性测试发现,2个目标分子TM2b和TM2d对于金葡菌ATCC14125的抑制活性强于所有测试的阳性对照药物;2个目标分子TM2m和TM2n对柑橘溃疡病菌的抑制率在浓度分别为0.5和0.2μg·mL^(-1)时都高于阳性对照链霉素,值得进一步研究。本研究首次合成了D-氨基葡萄糖与FQs拼合的新型分子,发现了超强抑菌活性分子,拓宽了D-氨基葡萄糖衍生物的类型及生物活性范围。Based on the idea of modification of sugar drugs,or transforming other active substances with sugar molecules,sixteen D-glucosamine-fluoroquinolone(FQ)derivatives were designed by combining Dglucosamine with FQs and synthesized by a multi-step reaction with shared intermediates.The assay results of antihuman pathogenic bacteria and anti-citrus canker showed that the inhibitory activities of two target molecules TM2b and TM2d against Staphylococcus aureus ATCC14125 were stronger than those of all tested positive control drugs,and the inhibitory rates of target molecules TM2m and TM2n against citrus canker were higher than that of the positive control streptomycin at the concentrations of 0.5 and 0.2µg·mL^(-1),respectively,which all were worthy of further study.In this study,a series of novel molecules composed of D-glucosamine and FQs were synthesized for the first time,and super antibacterial molecules were found,which expanded the types and biological activities of D-glucosamine derivatives.

关 键 词：D-氨基葡萄糖 氟喹诺酮 抗人致病菌活性 抗柑橘溃疡病菌活性 

分 类 号：R914[医药卫生—药物化学]