PDF(Pubmed)
Abstract：
Carbapenem antibiotic resistance is an emerging medical concern. Bacteria that possess the Klebsiella pneumoniae carbapenemase (KPC) protein, an enzyme that catalyzes the degradation of carbapenem antibiotics, have exhibited remarkable resistance to traditional and even modern therapeutic approaches. This study aimed to identify potential natural drug candidates sourced from the leaves of Artemisia judaica (A. judaica). The phytoconstituents present in A. judaica dried leaves were extracted using ethanol 80%. A reasonable amount of the extract was used to identify these phytochemicals via gas chromatography/mass spectrometry (GC/MS). One hundred twenty-two bioactive compounds from A. judaica were identified and subjected to docking analysis against the target bacterial protein. Four compounds (PubChem CID: 6917974, 159099, 628694, and 482788) were selected based on favorable docking scores (-9, -7.8, -7.7, and -7.5 kcal/mol). This computational investigation highlights the potential of these four compounds as promising antibacterial candidates against the specific KPC protein. Additionally, in vitro antibacterial assays using A. judaica extracts were conducted. The minimum inhibitory concentration (MIC) against the bacterium K. pneumonia was 125 μg/mL. Well-disk diffusion tests exhibited inhibition zones ranging from 10.3 ± 0.5 mm to 17 ± 0.5 mm at different concentrations, and time-kill kinetics at 12 h indicated effective inhibition of bacterial growth by A. judaica leaf extracts. Our findings have revealed the pharmaceutical potential of Artemisia judaica as a natural source for drug candidates against carbapenem-resistant pathogens.
摘要：
碳青霉烯类抗生素耐药性是一个新兴的医学问题。具有肺炎克雷伯菌碳青霉烯酶（KPC）蛋白的细菌，一种催化碳青霉烯类抗生素降解的酶，对传统甚至现代治疗方法表现出显著的抵抗力。这项研究旨在鉴定潜在的天然药物候选物，这些药物来自于犹太蒿的叶子（A.judaica).使用80％的乙醇提取柔道干燥叶中存在的植物成分。使用合理量的提取物通过气相色谱/质谱(GC/MS)鉴定这些植物化学物质。鉴定了来自A.judaica的122种生物活性化合物，并对其进行了针对目标细菌蛋白的对接分析。基于有利的对接评分(-9、-7.8、-7.7和-7.5kcal/mol)选择四种化合物(PubChemCID:6917974、159099、628694和482788)。该计算研究强调了这四种化合物作为针对特定KPC蛋白的有希望的抗菌候选物的潜力。此外,使用A.judaica提取物进行体外抗菌试验。对肺炎克雷伯菌的最小抑制浓度(MIC)为125μg/mL。井盘扩散试验在不同浓度下表现出10.3±0.5mm至17±0.5mm的抑制带,12h时的时间杀死动力学表明，柔道叶提取物可有效抑制细菌生长。我们的发现揭示了紫蒿作为抗耐碳青霉烯类病原体候选药物的天然来源的药物潜力。
