含膦酸酯肽的蛇床子素衍生物的合成与抗菌活性

doi:10.6023/cjoc202407015

研究论文

含膦酸酯肽的蛇床子素衍生物的合成与抗菌活性

杨家强^a,b,*, 周绪容^a, 陈阳密^a, 佘慧娴^a

^a遵义医科大学药学院遵义 563000;
^b遵义医科大学基础药理教育部重点实验室遵义 563000

收稿日期:2024-08-19 修回日期:2024-10-21
基金资助:
贵州省科技计划(黔科合基础-ZK[2024]一般265)和国家级大学生创新创业训练计划(202310661006)资助项目.

Synthesis and Antibacterial Activities of Osthole Derivatives Containing Phosphonateptide Fragment

Yang Jiaqiang^a,b,*, Zhou Xurong^a, Chen Yangmi^a, She Huixian^a

^aSchool of Pharmacy, Zunyi Medical University, Zunyi 563000;
^bKey Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi 563000

Received:2024-08-19 Revised:2024-10-21
Contact: * E-mail:yjqcn@126.com
Supported by:
Guizhou Provincial Science and Technology Plan (No. Qiankehe Foundation ZK[2024]265) and the National College Students' innovation and entrepreneurship training program(No. 202310661006).

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摘要/Abstract

在前期研究基础上,对具有潜在抗菌活性的蛇床子素衍生物进行结构优化,设计合成了21个含膦酸酯肽的新型衍生物,经¹H NMR、¹³C NMR和元素分析确证其结构。活性测试结果表明,(E)-(2-(4-(7-甲氧基-2-氧代-2H-色烯-8-基)-2-甲基丁-2-烯酰胺基)乙酰氨基)(3,4,5-三甲氧基苯基)甲基)膦酸二乙酯(5f)对金黄色葡萄球菌(S. aureus)、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)的最小抑菌浓度(MIC)分别为0.25、1、1和2 μg/mL,(E)-(2-(4-(7-甲氧基-2-氧代-2H-色烯-8-基)-2-甲基丁-2-烯酰胺基)乙酰氨基)(4-甲基噻唑-2-基)甲基)膦酸二乙酯(5u)对S. aureus、E. coli、MRSA和FREC的MIC分别为0.25、2、1和2 μg/mL,其抗菌活性优于对照药苯唑西林和诺氟沙星,可作为抗菌候选化合物进行深入研究。膦酸酯肽的结合,能提高其抗革兰氏阳性菌(S. aureus和MRSA)活性,并对革兰氏阴性菌(E. coli和FREC)有效。

关键词: 蛇床子素衍生物, 结构优化, 膦酸酯肽, 合成, 抗菌活性

Based on previous research, the structures of osthole derivatives with potential antibacterial activities were optimized. Twenty-one novel derivatives containing phosphonateptide were designed and synthesized, and confirmed by ¹H NMR, ¹³C NMR and elemental analysis. The antibacterial activities against S. aureus, E. coli, methicillin-resistant S. aureus(MRSA) and fluoroquinolone-resistant E. coli(FREC) were evaluated, the results showed that the minimum inhibitory concentration(MIC) of diethyl (E)- ((2-(4-(7-methoxy-2-oxo-2H-chromen-8-yl)-2-methylbut-2-enamido)acetamido)(3,4,5-trimethoxy phenyl)methyl)phosphonate (5f)was 0.25, 1, 1, 2 μg/mL respectively, and the MIC of diethyl (E)- ((2-(4-(7-methoxy-2-oxo- 2H-chromen-8-yl)-2-methylbut-2- enamido)acetamido)(4-methylthiazol-2-yl)methyl)phosphonate(5u)was 0.25, 2, 1, 2 μg/mL respectively. Its antibacterial activities were superior to the control drugs oxacillin and norfloxacin, which will be further developed as novel candidates for antibacterial drugs. The binding with phosphonateptide can enhance their anti-S. aureus and anti-MRSA activities, and keep significant anti-E. coli and anti-FREC activities.

Key words: osthole derivatives, structural optimization, phosphonateptide, synthesis, antibacterial activity

引用此文

杨家强, 周绪容, 陈阳密, 佘慧娴. 含膦酸酯肽的蛇床子素衍生物的合成与抗菌活性[J]. 有机化学, doi: 10.6023/cjoc202407015.

Yang Jiaqiang, Zhou Xurong, Chen Yangmi, She Huixian. Synthesis and Antibacterial Activities of Osthole Derivatives Containing Phosphonateptide Fragment[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202407015.

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