头孢噻肟的结构修饰及其体外抗菌活性变化

Modification and the in vitro antimicrobial activity of cefotaxime

[目的]头孢噻肟是第三代头孢菌素类抗生素,抗菌谱广,对革兰氏阴性菌G-作用较好,但对革兰氏阳性菌G+,如金黄色葡萄球菌(Staphylococcus aureus,S.a)等活性较弱。头孢噻肟的母核是7-氨基头孢烷酸(7-ACA),对其活性基团7位氨基进行修饰,考查抗G+的活性。[方法]以戊二醛作为偶联剂在头孢噻肟的7位氨基上偶联壳聚糖,并利用红外光谱进行表征,以流式细胞术检测到的荧光强度或碘化丙锭(PI)染色细胞百分率(PI%,被PI染色的细胞比例)为度量指标。[结果]S.a与修饰的头孢噻肟作用后荧光强度明显增加,修饰前后头孢噻肟的样品PI%分别为28.9%、68.8%,可见头孢噻肟修饰后对S.a的活性大大增强。[结论]修饰后的头孢噻肟与S.a作用后的样品荧光强度增加了近40%,由此推测头孢噻肟的7位氨基是一种很有前途的提高杀菌效果的活性基团。

[Objective]Cefotaxime is the third generation antibiotics of semisythesized cephalosporin with a broad antibacterial spectrum.It has strong effect on Gram negative bacteria(G-),however,its effect on Gram positive bacteria(G+),such as Staphylococcus aureus is weaker.The nuclear of the drug is 7-aminocephalosporanic acid(7-ACA)and the amino at the 7-side is active radical.In order to investigate whether the modification of amido at the 7-side chain of cefotaxime can improves its effect on G+,such as Staphylococcus aureus(S.a),the cefotaxime is modified.[Method]The cefotaxime is modified with chitosan via glutaric dialdehyde and corroborated the modification result by infrared spectroscopy,then with fluorescence intensity or the percentage of PI-stained cells(the proportion of cells stained by propidium iodide,PI%)which is detected by flow cytometer to evaluate the antimicrobial activity of the modified and non-modified cefotaxime sodium on S.a.[Result]The fluorescence intensity of S.a treated by the modified cefotaxime is enhanced significantly.The PI%of the modified cefotaxime is 68.8%and the cefotaxime is only 28.9%,that is the PI%increased nearly 40%.In conclusion,the antimicrobial activity of the modified cefotaxime is enhanced.[Conclusion]The modified amido of cefotaxime is perhaps a promising active radical in upgrading bactericidal effect.