一个6-胺基-β-环糊精衍生物的合成及其与哌拉西林所组成的复合物的体外抗菌活性增效作用

摘要

Objective The 6-side chain of β-cyclodextrin (β-CD) in an appropriate "length and more hydrophobic could increase the ability of complexation and capability of the cavity that the molecule of guest drug would be fully protected.For this complex property,per-6-octylamino-6-deoxy-β-cyclodextrin HCl salt (1)has been synthesized.Methods Complex of 1 with β-lactam-antibiotic piperacillin has been also investigated through 1H-NMR experiments.Analysis of 1H-NMR data resulted in the indication that the part of β-lactam group of piperacillin was inserted into the cavity of 1 and that the whole molecule was protected.Results To exam the antibacterial activity with the β-CD derivative 1,piperacillin has been tested in vitro with and without compound 1 against resistant strains Methicillin-resistant Staphylococcus aureus (MRSA).The minimal inhibition concentration (MIC) of piperacillin with 1 against MRSA in vitro appeared to be 4.0～8.0μg/mL at a molar ratio of 1:1 piperacillincompound 1 compared with ＞128.0μg/mL without 1.Conclusion Those results indicated that derivative 1 had strong potentiation ofpiperacillin against MRSA.%目标 β-环糊精6位取代基链适当的”长度”及其较强的疏水性能提高其”内洞”与客体药物分子形成复合(包合)物的能力,使其药物分子能够得到充分保护.依据这种性能,化学合成了β-环糊精衍生物6-辛基胺基-6-去氧-β-环糊精盐酸盐(1).方法 通过核磁共振氢谱(1H-NMR)实验,对化合物1与β-内酰胺类抗生素哌拉西林所组成的复合物进行了研究.研究结果表明,哌拉西林分子中的β-内酰胺内核被嵌入化合物1分子的内洞中,从而使哌拉西林分子得到保护.结果 哌拉西林与化合物1合用前后对耐甲氧西林金葡菌(MRSA)等9种细菌的抗菌作用进行了测定.测定结果显示,哌拉西林与化合物1合用前后对耐甲氧西林金葡菌的体外最低抑菌浓度(MIC)分别为＞128μg/mL及4.0～8.0μg/mL.结论 研究结果表明化合物1对哌拉西林体外抗耐甲氧西林金葡菌具有较强的抗菌活性恢复和增效作用.