含L-苯丙氨酸结构的蛇床子素衍生物的合成与抗菌活性  

Synthesis and Antibacterial Activities of Osthole Derivatives Containing L-Phenylalanine

作　　者：周绪容 陈阳密 佘慧娴 杨家强 ZHOU Xurong;CHEN Yangmi;SHE Huixian;YANG Jiaqiang(School of Pharmacy,Zunyi Medical University,Zunyi 563000,China;Qianxinan Autonomous Prefecture Hospital of Traditional Chinese Medicine,Xingyi 562400,China)

机构地区：[1]遵义医科大学药学院,贵州遵义563000 [2]黔西南州中医院,贵州兴义562400

出　　处：《中国药学杂志》2025年第4期326-333,共8页Chinese Pharmaceutical Journal

基　　金：贵州省科技计划项目资助(科合基础-ZK[2024]一般265);国家级大学生创新创业训练计划项目资助(202310661006)。

摘　　要：目的对前期抗菌活性化合物进行结构改造与优化。方法首先,以蛇床子素为原料,分别经SeO_(2)和NaClO_(2)/NaH_(2)PO_(4)氧化,合成中间体2;接着,Boc-L-苯丙氨酸和胺通过缩合、脱保护,制得中间体3;然后,中间体2与中间体3再缩合制得目标物;最后,采用两倍稀释法对目标物进行体外抗菌活性测试。结果合成了22个目标化合物,经核磁共振波谱法(NMR)和元素分析确认结构;该类化合物对所测试细菌有较好抑制作用,化合物4o和4q的抗大肠杆菌(E.coli)、耐甲氧西林金黄色葡萄球菌(MRSA)和耐氟喹诺酮大肠杆菌(FREC)活性最为显著,前者的最小抑菌浓度(MIC)分别为2、16和4μg·mL^(-1),后者的MIC分别为4、16和8μg·mL^(-1),优于阳性对照药苯唑西林(16、256和64μg·mL^(-1))。结论部分目标物对革兰阳性菌和阴性菌有较显著抑制作用,L-苯丙氨酸的引入,有助于提升抗革兰阴性菌活性。OBJECTIVE To modify and optimize the structure of osthole derivatives with better antibacterial activities.METHODS First,intermediate 2 was synthesized by oxidation of SeO_(2)and NaClO_(2)/NaH_(2)PO_(4)using osthole extract as raw material.Next,intermediate 3 was synthesized through condensation reaction of Boc-L-phenylalanine and amines,followed by deprotection reaction.Then,the target compounds were prepared by recondensing intermediate 2 and 3.Finally,the antibacterial activities of the products were tested by the agar dilution method.RESULTS Twenty-two osthole derivatives were synthesized,and their structures were confirmed by NMR and elemental analysis.The results showed that these compounds had better inhibitory effects on the tested bacteria.The activities of compounds 4o and 4q against E.coli,MRSA and FREC were the most significant,the MIC of 4o was 2,16,and 4μg·mL^(-1)respectively,and the MIC of 4q was 4,16,and 8μg·mL^(-1)respectively,which were superior to that of the control drug oxacillin.CONCLUSION Some derivatives have significant inhibitory effects on both gram-positive and negative bacteria.The introduction of L-phenylalanine into the structure of osthole can enhance its anti-gram-negative bacteria activities.

关 键 词：蛇床子素衍生物 L-苯丙氨酸 结构优化 合成 抗菌活性 

分 类 号：R914[医药卫生—药物化学]