Characterization of the interactions of human serum albumin (HSA), gatifloxacin, and metronidazole using spectroscopic and electrochemical methods

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• 作者：Li Fu ; ^{fuli668@126.com" class="auth_mail} ; Xiu-fen Liu ; Qiu-xiang Zhou ; Ji-xiang Zhang ; Jing-ya Dong ; Jian-fang Wang
• 关键词：Fluorescence spectroscopy ; UV-spectroscopy ; Electrochemical ; Gatifloxacin ; Metronidazole ; Human serum albumin
• 刊名：Journal of Luminescence
• 出版年：May, 2014
• 年：2014
• 卷：149
• 期：Complete
• 页码：208-214
• 全文大小：620 K

文摘

Human serum albumin (HSA), the most abundant protein in blood plasma, is an important carrier for many drugs. Understanding HSA-drug interactions is critical in being able to interpret the distribution and acting mechanisms of these drugs, which is particularly important in the case of multi-drug therapy. In this study, we investigated the interactions between HSA and two commonly used antibiotics, gatifloxacin (GFLX) and metronidazole (MET), in Tris-HCl buffer solution (pH=7.4). The efficacy of the individual drugs (GFLX or MET) and the efficacy of a combination of GFLX and MET were measured using fluorescence spectroscopy, UV absorption spectroscopy, and electrochemical methods. Our results demonstrated that GFLX and MET have a synergistic effect. Briefly, one drug decreased the binding stability with HSA of the other drug, thus increasing the concentration of free drug at the action sites. The interaction of drugs with HSA is a process of complex-formation static quenching. There is approximately one binding site between HSA and the drug (GFLX or MET). The binding distance, r, between the drug and HSA was determined on the basis of the theory of Forster-type non-radiative energy transfer. It was shown that the interaction between the two drugs increased the r-value. Using thermodynamic parameters, we found that the binding of drug-HSA interactions is mainly controlled by electrostatic force. Analysis of the synchronous fluorescence spectrum suggested that the interactions between the drugs have important effects on protein conformation. In conclusion, combining GFLX and MET enhances treatment efficacy. Our study provides a basis to understand the mechanism of the interaction of MET, GFLX and HSA in the human body.