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目标β-环糊精衍生物6位上取代基的“大小”及其疏水性能影响其与药物分子形成复合(包合)物的能力。依据这种特性,6-(4-甲氧基苄基)-胺基-β-环糊精作为主体化合物可以能够与抗生素分子形成一定形状和构象的特殊复合物,并因此可以使抗生素对耐药菌的抗菌活性起到增效作用。方法以β-环糊精为初始原料,合成了具有水溶性的β-环糊精衍生物6-(4-甲氧基苄基)-胺基-β-环糊精盐酸盐(1)。通过核磁共振氢谱(1H-NMR)分析方法,对化合物1与β-内酰胺类抗生素哌拉西林在0.9%生理盐水中所形成的复合物的形状和构象进行了研究和探讨。同时,化合物1对哌拉西林体外抗耐药菌株粪肠球菌(E.faecium)、铜绿假单胞菌(P.aeruginosa)及耐甲氧西林金葡菌(MRSA)的增效作用进行了测定。结果哌拉西林与化合物1形成复合物前后对粪肠球、菌铜绿假单胞菌和耐甲氧西林金葡菌的体外最低抑菌浓度(MIC)分别为>128及16~32μg/mL,1.8~8.0μ/mL。结论化合物1对哌拉西林体外抗耐药菌株具有较强的抗菌活性恢复和增效作用。
The “size” of the substituent at position 6 of the target β-cyclodextrin derivative and its hydrophobicity can affect its ability to form complex (inclusion) products with the drug molecule. According to this property, 6- (4-methoxybenzyl) -amino-β-cyclodextrin, as a host compound, can be capable of forming specific complexes of certain shapes and conformations with antibiotic molecules and thus can make antibiotic resistance Bacteria antibacterial activity play a synergistic effect. Methods 6- (4-methoxybenzyl) -amino-β-cyclodextrin hydrochloride (1) with water-soluble β-cyclodextrin was synthesized using β-cyclodextrin as the starting material. The shape and conformation of complex formed by compound 1 and β-lactam antibiotics piperacillin in 0.9% physiological saline were studied by 1H NMR. At the same time, the synergistic effects of compound 1 against E. faecium, P. aeruginosa and MRSA in vitro against piperacillin were determined . Results The minimum inhibitory concentration (MIC) of Enterococcus faecalis, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus before and after the compound of piperacillin and compound 1 were> 128 and 16 ~ 32μg / mL respectively, 1.8 ~ 8.0μ / mL. Conclusion Compound 1 has strong antibacterial activity recovery and synergistic effect against piperacillin resistant strains in vitro.