Background: Pipemidic acid is a broad-spectrum quinolone antibacterial agent for the treatment of chronic urinary tract infections against both gram-positive and gram-negative bacteria. Both quinolone and fluoroquinolone antibiotics have been useful in combating bacterial infections. However, patients suffer severe side effects when they stop taking the medication. The piperazinyl region of pipemidic acid is highly responsible for the side effects.

Objective: The objective of this study is to design new compounds in which the piperazinyl region is masked by way of conjugation to benzoic acid derivatives.

Methods: In silico studies were conducted using AutoDockTools software for ligand-protein docking. The docking scores were compared to the parent pipemidic acid docked to Bacterial DNA (deoxyribonucleic acid) gyrase and GABA (gamma-Aminobutyric acid) receptor from the PDB (Protein Data Bank) database. Sites of metabolism, biological activity, quantum chemical descriptors, and ADME (absorption, distribution, metabolism, and excretion) property predictions for each designed ligand were also evaluated.

Results: The docking studies and biological activity predictions showed good anti-infective properties (ligand PAR03) whilst also suggesting a reduction in GABA receptor agonist activity. The performance of PAR03 correlates with its electronic properties showing electrophilic character (can generate Reactive Electrophilic Species (RES)).

Conclusion: The results from this study indicate that modification of the piperazinyl region of pipemidic acid can be an effective way to improve the drug potency whilst also ensuring reduction of the associated side effects.

背景：哌啶酸是一种广谱喹诺酮类抗菌剂，用于治疗针对革兰氏阳性和革兰氏阴性细菌的慢性尿路感染。喹诺酮和氟喹诺酮抗生素均已用于对抗细菌感染。然而，当患者停止服药时，他们会遭受严重的副作用。哌啶酸的哌嗪基区域是造成副作用的主要原因。

目的：本研究的目的是设计新化合物，其中哌嗪基区域通过与苯甲酸衍生物结合而被掩盖。

方法：使用AutoDockTools软件进行计算机模拟研究，以进行配体-蛋白质对接。将对接得分与来自PDB（蛋白质数据库）数据库中对接的细菌DNA（脱氧核糖核酸）促旋酶和GABA（γ-氨基丁酸）受体的亲代哌啶酸进行比较。还评估了每种设计配体的代谢位点，生物活性，量子化学描述符和ADME（吸收，分布，代谢和排泄）特性预测。

结果：对接研究和生物学活性预测显示出良好的抗感染特性（配体PAR03），同时还表明GABA受体激动剂活性降低。PAR03的性能与其显示亲电子特性的电子性能相关（可以生成反应性亲电子物种（RES））。

结论：这项研究的结果表明，对哌啶酸的哌嗪基区域进行修饰可以是提高药效的有效方法，同时还可以确保减少相关的副作用。