Antibacterial drugs have been widely used for the past century to treat diseases, but their efficacy has been limited by multi-resistant pathogens, particularly those that utilize beta-lactamase enzymes. The inhibition of beta-lactamase enzymes holds great promise for reducing the influence of such pathogens. This study aims to evaluate the mechanism of inhibition of phytochemicals with antibacterial activity against two classes of beta-lactamases using computational methods. Methods: To achieve this objective, a total of thirty phytochemicals were docked against SHV-1 beta-lactamase and AmpC beta-lactamase after procurement from Protein Data Bank. The pharmacokinetics (ADMET) and density functional theory (DFT) analysis study were also conducted to unravel the nature of the top six most promising compounds on each protein. The results showed that a significant percentage of the compounds had binding affinities greater than that of avibactam, the positive control. Quercetin-3-O-rutinoside showed the most promising results against SHV-1 beta-lactamase with an affinity of −9.4 kcal/mol, while luteolin was found to be the most promising candidate against AmpC beta-lactamase with an affinity of −8.5 kcal/mol. DFT analysis demonstrated the reactivity of these compounds, and the ADMET study indicated that they were relatively safe. In conclusion, the study's findings suggest that the selected compounds have significant potential to inhibit beta-lactamase and may be used in combination with antibiotics against organisms that produce beta-lactamase. This study provides a basis for further research in a wet-lab setting to validate the results.

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通过计算机辅助方法鉴定对 β-内酰胺酶具有抑制潜力的植物化学物质

过去一个世纪以来，抗菌药物已被广泛用于治疗疾病，但其功效受到多重耐药病原体的限制，特别是那些利用β-内酰胺酶的病原体。 β-内酰胺酶的抑制对于减少此类病原体的影响具有很大的希望。本研究旨在利用计算方法评估对两类 β-内酰胺酶具有抗菌活性的植物化学物质的抑制机制。方法：为了实现这一目标，从蛋白质数据库采购了总共 30 种植物化学物质，与 SHV-1 β-内酰胺酶和 AmpC β-内酰胺酶进行对接。还进行了药代动力学 (ADMET) 和密度泛函理论 (DFT) 分析研究，以揭示每种蛋白质最有希望的六种化合物的性质。结果表明，很大一部分化合物的结合亲和力高于阳性对照阿维巴坦。 Quercetin-3-O-rutinoside 对 SHV-1 β-内酰胺酶显示出最有希望的结果，亲和力为 -9.4 kcal/mol，而木犀草素被发现是针对 AmpC β-内酰胺酶最有希望的候选物，亲和力为 -8.5千卡/摩尔。 DFT 分析证明了这些化合物的反应活性，ADMET 研究表明它们相对安全。总之，该研究的结果表明，所选化合物具有抑制 β-内酰胺酶的巨大潜力，并且可以与抗生素联合使用来对抗产生 β-内酰胺酶的生物体。这项研究为在湿实验室环境中进一步研究以验证结果提供了基础。