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首页> 外文期刊>RSC Advances >The binding of free and copper-complexed fluoroquinolones to OmpF porins: an experimental and molecular docking study
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The binding of free and copper-complexed fluoroquinolones to OmpF porins: an experimental and molecular docking study

机译：游离和铜络合的氟喹诺酮类与OmpF孔蛋白的结合：实验和分子对接研究

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Bacterial resistance is a critical public health issue and the development of alternative antibiotics to counteract this problem is an urgent matter. Fluoroquinolones are widely used antibiotics and numerous cases of bacterial resistance to these drugs have already been reported. One important mechanism of resistance is the decrease of the permeability of the bacterial membrane to antibiotics by mutation of the OmpF porin. Fluoroquinolone complexation with copper and a nitrogen-donor heterocyclic ligand is an approach developed to counteract this mechanism of bacterial resistance. The binding of antibiotics to the constriction zone residues of porins has been shown to be essential for their influx across the channel. In the present work, the interaction of sparfloxacin, ciprofloxacin and their respective copper ternary complexes with the outer-membrane protein F (OmpF) porin was studied to further explore the channel selectivity for each of these molecules. Surface plasmon resonance was used to determine the association constants between the drugs and the OmpF protein and molecular docking was used to further analyze the interaction between them. The results support a higher affinity of free fluoroquinolones to the constriction zone of the OmpF channel, when compared to the respective copper-complexes. The findings of this work provide insights that will be helpful to proceed with the study of metal-complexes as alternatives to free fluoroquinolones in resistant infections, avoiding the high-cost and time-consuming processes of discovering and designing new antibiotics.
机译：细菌耐药性是一个关键的公共卫生问题，开发替代抗生素以解决该问题是当务之急。氟喹诺酮类药物是广泛使用的抗生素，并且已经报道了许多对这些药物产生细菌耐药性的情况。耐药的一个重要机制是通过OmpF孔蛋白的突变降低细菌膜对抗生素的渗透性。氟喹诺酮与铜和氮供体杂环配体的络合是一种抵消这种细菌耐药性机制的方法。业已证明，抗生素与孔蛋白的收缩区残基的结合对于其跨通道流入至关重要。在目前的工作中，研究了司帕沙星，环丙沙星及其各自的铜三元复合物与外膜蛋白F（OmpF）孔蛋白的相互作用，以进一步探索这些分子中每个分子的通道选择性。表面等离振子共振用于确定药物与OmpF蛋白之间的缔合常数，分子对接用于进一步分析它们之间的相互作用。与相应的铜络合物相比，结果支持游离氟喹诺酮类对OmpF通道收缩区的亲和力更高。这项工作的发现提供了有益的见识，将有助于继续开展金属复合物的研究，以替代耐药性感染中游离氟喹诺酮类药物，从而避免了发现和设计新抗生素的高成本且费时的过程。

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