Faculty of Applied sciences and Biotechnology, Shoolini University, Solan 173212, India.
DNA Lab's Center for Applied Sciences, Dehradun 248001, Uttarakhand, India.
Molecules. 2022 Aug 5;27(15):4971. doi: 10.3390/molecules27154971.
Urinary tract infections (UTIs) are becoming more common, requiring extensive protection from antimicrobials. The global expansion of multi-drug resistance uropathogens in the past decade emphasizes the necessity of newer antibiotic treatments and prevention strategies for UTIs. Medicinal plants have wide therapeutic applications in both the prevention and management of many ailments. is a medicinal plant that is found in the warmer and wetlands regions of the world. It has been used in Ayurvedic systems for centuries. The present study aimed to investigate the antibacterial potential of the extract of leaves and its bioactive molecules against UTIs that are caused by and . This in vitro experimental study was conducted by an agar well diffusion method to evaluate the antimicrobial effect of 80% methanol, 96% ethanol, and aqueous extracts of leaves on uropathogens. Then, further screening of their phytochemicals was carried out using standard methods. To validate the bioactive molecules and the microbe interactions, AutoDock Vina software was used for molecular docking with the fosfomycin resistance protein (5WEW) and the Zn-dependent receptor-binding domain of MR/P fimbrial adhesin MrpH (6Y4F). Toxicity prediction and drug likeness were predicted using ProTox-II and Molinspiration, respectively. A molecular dynamics (MD) simulation was carried out to study the protein ligand complexes. The methanolic leaves extract of revealed a 22.3 mm ± 0.6 mm to 25.0 mm ± 0.5 mm inhibition zone, while ethanolic extract seemed to produce 19.3 mm ± 0.8 mm to 23.0 mm ± 0.4 mm inhibition zones against with the use of increasing concentrations. In the case of activity, the methanolic extracts showed a 21.0 mm ± 0.8 mm to 24.0 mm ± 0.6 mm zone of inhibition and the ethanol extract produced a 17.0 mm ± 0.9 mm to 23.0 mm ± 0.7 mm inhibition zone with increasing concentrations. Carbohydrates, flavonoids, saponin, phenolic, and terpenoid were common phytoconstituents identified in extracts. Oroxindin showed the best interactions with the binding energies with 5WEW and 6Y4F, -7.5 kcal/mol and -7.4 kcal/mol, respectively. Oroxindin, a bioactive molecule, followed Lipinski's rule of five and exhibited stability in the MD simulation. The overall results suggest that Oroxindin from can be a potent inhibitor for the effective killing of and . Additionally, its safety has been established, indicating its potential for future drug discovery and development in the treatment for UTIs.
尿路感染（UTIs）越来越常见，需要广泛使用抗生素进行保护。过去十年中，全球范围内多药耐药尿路病原体的扩张强调了需要新的抗生素治疗方法和预防策略来治疗 UTIs。药用植物在预防和治疗许多疾病方面具有广泛的治疗应用。 是一种药用植物，分布在世界上温暖和湿地地区。它在阿育吠陀系统中已经使用了几个世纪。本研究旨在研究 叶提取物及其生物活性分子对由 和 引起的 UTIs 的抗菌潜力。这项体外实验研究通过琼脂孔扩散法进行，以评估 80%甲醇、96%乙醇和 叶水提物对尿路病原体的抗菌作用。然后，使用标准方法进一步筛选其植物化学物质。为了验证生物活性分子和微生物的相互作用，使用 AutoDock Vina 软件对 膦酸酯耐药蛋白（5WEW）和 Zn 依赖性受体结合结构域的 MR/P 菌毛粘附素 MrpH（6Y4F）进行分子对接。使用 ProTox-II 和 Molinspiration 分别预测毒性和药物相似性。进行分子动力学（MD）模拟以研究蛋白质配体复合物。 甲醇叶提取物对 显示出 22.3mm±0.6mm 至 25.0mm±0.5mm 的抑制带，而随着浓度的增加，乙醇提取物似乎对 产生 19.3mm±0.8mm 至 23.0mm±0.4mm 的抑制带。在 活性方面，甲醇提取物显示出 21.0mm±0.8mm 至 24.0mm±0.6mm 的抑制带，而乙醇提取物随着浓度的增加产生 17.0mm±0.9mm 至 23.0mm±0.7mm 的抑制带。碳水化合物、类黄酮、皂苷、酚类和萜类是在 提取物中鉴定出的常见植物成分。氧化吲哚与 5WEW 和 6Y4F 的结合能分别为-7.5kcal/mol 和-7.4kcal/mol，显示出与结合的最佳相互作用。氧化吲哚是一种生物活性分子，遵循 Lipinski 的五规则，在 MD 模拟中表现出稳定性。总体结果表明， 中的氧化吲哚可以成为有效杀死 和 的有效抑制剂。此外，它的安全性已经建立，表明它有可能成为未来治疗 UTIs 的药物发现和开发的候选药物。
