为了获取抗菌候选化合物, 运用药效片段组合原理, 以天然产物蛇床子素为苗头化合物, 设计合成了26个含噻唑片段的蛇床子素衍生物, 经¹H NMR、¹³C NMR和元素分析确证其结构. 抗菌活性测试结果表明, 2-{[8-(3-甲基丁-2-烯-1-基)-2-氧代-2H-色烯-7-基]氧基}-N-(4-邻氟苯基噻唑-2-基)乙酰胺(5g)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2、4、2和4 μg/mL, 2-{[8-(3-甲基丁-2-烯-1-基)-2-氧代-2H-色烯-7-基]氧基}-N-(4-环丙基噻唑-2-基)乙酰胺(5w)对S. aureus、E. coli、MRSA和FREC的MIC分别为2、2、4和4 μg/mL, 2-{[8-(3-甲基丁-2-烯-1-基)-2-氧代-2H-色烯-7-基]氧基}-N-[(2,4'-双噻唑)-2'-基]乙酰胺(5x)对S. aureus、E. coli、MRSA和FREC的MIC分别为1、2、2和2 μg/mL. 其抗S. aureu活性与对照药苯唑西林基本相当, 优于对照药诺氟沙星; 抗E. coli、MRSA和FREC优于对照药苯唑西林和诺氟沙星. 噻唑片段的引入能提高蛇床子素衍生物的抗菌活性.

In order to obtain antibacterial candidate compounds, using the principle of pharmacodynamic fragment combination, the thiazole fragment was introduced into the structure of the seedling compound osthole. Twenty-six osthole derivatives 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 concentrations (MICs) of N-(4-(2-fluorophenyl)thiazol-2-yl)-2-((8-(3-methyl- but-2-en-1-yl)-2-oxo-2H-chromen-7-yl)oxy)acetamide (5g) were 2, 4, 2, 4 μg/mL, respectively. The MICs of N-(4-cyclo- propylthiazol-2-yl)-2-((8-(3-methylbut-2-en-1-yl)-2-oxo-2H-chromen-7-yl)oxy)acetamide (5w) were 2, 2, 4, 4 μg/mL, respectively. The MICs of N-([2,4'-bithiazol]-2'-yl)-2-((8-(3-methylbut-2-en-1-yl)-2-oxo-2H-chromen-7-yl)oxy)acetamide (5x) were 1, 2, 2, 2 μg/mL. respectively. Their anti-S. aureu activities were comparable to the control drug oxacillin and superior to norfloxacin, and anti-E. coli, MRSA, and FREC were superior to the control drugs oxacillin and norfloxacin. The connection of thiazole fragment to the structure of osthole can effectively enhance antibacterial activities.