Requimte, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal.
J Membr Biol. 2011 Jun;241(3):117-25. doi: 10.1007/s00232-011-9368-4. Epub 2011 May 17.
Probing drug/lipid interactions at the molecular level represents an important challenge in pharmaceutical research, drug discovery and membrane biophysics. Previous studies showed that enrofloxacin metalloantibiotic has potential as an antimicrobial agent candidate, since it exhibits antimicrobial effect comparable to that of free enrofloxacin but a different translocation route. These differences in uptake mechanism can be paramount in counteracting bacterial resistance. In view of lipids role in bacterial drug uptake, the interaction of these compounds with different Escherichia coli model membranes were studied by fluorescence spectroscopy. Partition coefficients determined showed that lipid/antibiotic interactions were sensitive to liposomes composition and that the metalloantibiotic had a higher partition than free enrofloxacin. These results corroborate the different mechanism of entry proposed and can be rationalized on the basis that an electrostatic interaction between the metalloantibiotic positively charged species, present at physiological pH, and the lipids negatively charged head groups clearly promotes the lipid/antimicrobial association.
在分子水平上探测药物/脂质相互作用是药物研究、药物发现和膜生物物理学的一个重要挑战。先前的研究表明，恩诺沙星金属抗生素具有作为候选抗菌剂的潜力，因为它表现出与游离恩诺沙星相当的抗菌效果，但具有不同的转运途径。这些摄取机制的差异在对抗细菌耐药性方面可能至关重要。鉴于脂质在细菌药物摄取中的作用，通过荧光光谱法研究了这些化合物与不同大肠杆菌模型膜的相互作用。确定的分配系数表明，脂质/抗生素相互作用对脂质体组成敏感，并且金属抗生素的分配系数高于游离恩诺沙星。这些结果证实了所提出的不同进入机制，并且可以基于在生理 pH 下存在的金属抗生素带正电荷物种与脂质带负电荷头部基团之间的静电相互作用，清楚地促进了脂质/抗生素的缔合，从而合理化。
