含膦酸酯肽的蛇床子素衍生物的合成与抗菌活性
收稿日期: 2024-08-19
修回日期: 2024-10-21
网络出版日期: 2024-10-29
基金资助
贵州省科技计划(黔科合基础-ZK[2024]一般265); 国家级大学生创新创业训练计划(202310661006)
Synthesis and Antibacterial Activities of Osthole Derivatives Containing Phosphonateptide Fragment
Received date: 2024-08-19
Revised date: 2024-10-21
Online published: 2024-10-29
Supported by
Guizhou Provincial Science and Technology Plan (Qiankehe Foundation ZK[2024]265); National College Students? Innovation and Entrepreneurship Training Program(202310661006)
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. 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、1.00、1.00和2.00 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、2.00、1.00和2.00 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.
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, 2025 , 45(4) : 1306 -1314 . DOI: 10.6023/cjoc202407015
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. 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 concentrations (MICs) 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) were 0.25, 1.00, 1.00, 2.00 μg/mL respectively, and the MICs 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) were 0.25, 2.00, 1.00, 2.00 μg/mL, respectively. Its antibacterial activities were superior to the control drugs of 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.
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