A three-dimensional quantitative structure-activity relationship (3D-QSAR) model was established based on molecular structures and docking scores (representing the biodegradability); the scores were obtained for 23 fluoroquinolones (FQs) and the oxidoreductase (PDB ID: 1YZP) of Phanerochaete chrysosporium in the aerobic process of municipal wastewater treatment plants. In the Comparative Molecular Field Analysis (CoMFA) model, q2 was 0.516 and r2pred was 0.727, which showed that the model was reliable and robust. The modification information obtained by the contour maps showed that introducing electronegative, bulky or electropositive groups at different active sites could increase the biodegradability of fluoroquinolone derivatives. Using levofloxacin (LEV) as a modified molecule, 35 fluoroquinolone derivatives with higher biodegradability than LEV were designed. After the evaluation of genotoxicity, bioconcentration and photodegradation, Derivative-15, with higher biodegradability (increased by 27.85%), higher genotoxicity, higher photodegradation and lower bioconcentration, was identified as the most environmentally friendly fluoroquinolone derivative. The 2D-QSAR model of FQ biodegradability was established through the quantization parameters, and q+ was identified as the main parameter affecting the biodegradability of FQs through sensitivity analysis. In addition, the docking results of LEV and Derivative-15 with the oxidoreductase in P. chrysosporium showed that the electrostatic field force between Derivative-15 and the amino acid residues promoted the binding of the donor to the receptor protein, thereby increasing the biodegradability of Derivative-15. Additionally, molecular dynamics simulations revealed that the enhancement of the electrostatic field force with Derivative-15 could promote the binding of the ligand to the receptor, which was basically consistent with the conclusion of molecular docking. Finally, the three microbial degradation pathways of LEV and Derivative-15 were also proposed. The total energy barrier value of the pathway with the lowest total energy barrier of biodegradation was reduced by 32.07%, which was basically consistent with the enhancement of biodegradability of Derivative-15.

中文翻译：

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使用3D-QSAR模型和生物降解途径分析设计的高度可生物降解的氟喹诺酮衍生物。

基于分子结构和对接分数（代表生物降解性）建立了三维定量构效关系（3D-QSAR）模型。在城市污水处理厂的好氧工艺中，获得了23个氟喹诺酮类（FQs）和Phanerochaete chrysosporium氧化还原酶（PDB ID：1YZP）的分数。在比较分子场分析（CoMFA）模型中，q2为0.516，r2pred为0.727，表明该模型可靠且可靠。通过等高线图获得的修饰信息表明，在不同的活性位点引入电负性，大体积或正电性基团可以提高氟喹诺酮衍生物的生物降解能力。使用左氧氟沙星（LEV）作为修饰分子，设计了35种比LEV具有更高生物降解性的氟喹诺酮衍生物。在对遗传毒性，生物浓度和光降解性进行评估后，具有较高生物降解性（增加27.85％），较高的遗传毒性，较高的光降解性和较低的生物浓度的衍生物15被确定为最环保的氟喹诺酮衍生物。通过量化参数建立了FQ生物降解性的二维QSAR模型，并通过敏感性分析将q +确定为影响FQs生物降解性的主要参数。此外，LEV和Derivative-15与金孢假单胞菌中的氧化还原酶的对接结果表明，Derivative-15和氨基酸残基之间的静电场力促进了供体与受体蛋白的结合，从而提高了衍生物15的生物降解能力。此外，分子动力学模拟表明，用Derivative-15增强静电场力可以促进配体与受体的结合，这与分子对接的结论基本一致。最后，还提出了LEV和Derivative-15的三种微生物降解途径。具有最低生物降解总能垒的路径的总能量垒值降低了32.07％，这与衍生15的生物降解能力的提高基本一致。这与分子对接的结论基本一致。最后，还提出了LEV和Derivative-15的三种微生物降解途径。具有最低生物降解总能垒的路径的总能量垒值降低了32.07％，这与衍生15的生物降解能力的提高基本一致。这与分子对接的结论基本一致。最后，还提出了LEV和Derivative-15的三种微生物降解途径。具有最低生物降解总能垒的路径的总能量垒值降低了32.07％，这与衍生15的生物降解能力的提高基本一致。