当前位置：
X-MOL 学术
›
J. Nat. Prod.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Identification of Privileged Antichlamydial Natural Products by a Ligand-Based Strategy
Journal of Natural Products ( IF 3.3 ) Pub Date : 2017-10-18 00:00:00 , DOI: 10.1021/acs.jnatprod.6b01052 Elina Karhu 1 , Janne Isojärvi 2 , Pia Vuorela 1 , Leena Hanski 1 , Adyary Fallarero 1
Journal of Natural Products ( IF 3.3 ) Pub Date : 2017-10-18 00:00:00 , DOI: 10.1021/acs.jnatprod.6b01052 Elina Karhu 1 , Janne Isojärvi 2 , Pia Vuorela 1 , Leena Hanski 1 , Adyary Fallarero 1
Affiliation
|
The obligate intracellular pathogen Chlamydia pneumoniae remains a difficult target for antimicrobial therapy. Owing to the permeability barrier placed by bacterial and host vacuolar membranes, as well as the propensity of the bacterium for persistent infections, treatment failures are common. Despite the urgent need for new antichlamydial compounds, their discovery is challenged by the technically demanding assay procedures and lack of validated targets. An alternative strategy of using naturally occurring compounds and their derivatives against C. pneumoniae is presented. The strategy consists of the application of ligand-based virtual screening to a natural product library of 502 compounds with the ChemGPS-NP chemography tool followed by in vitro antichlamydial assays. The reference set used for the 2D similarity search was constructed of 19 known antichlamydial compounds of plant origin. Based on the similarity screen, 53 virtual hits were selected for in vitro testing. Six compounds (leads) were identified that cause ≥50% C. pneumoniae growth inhibition and showed no impact on host cell viability. The leads fall into completely new antichlamydial chemotypes, one of them being mycophenolic acid (IC50 value 0.3 μM). The outcome indicates that using this flipped, target-independent strategy is useful for facilitating the antimicrobial lead discovery against challenging microbes.
中文翻译：
基于配体的策略识别特权衣原体天然产物
专心的细胞内病原体肺炎衣原体仍然是抗微生物治疗的困难目标。由于细菌和宿主液泡膜所设置的通透性屏障，以及细菌对持续感染的倾向，治疗失败是常见的。尽管迫切需要新的抗衣原体化合物，但其发现受到技术要求高的测定程序和缺乏经过验证的靶标的挑战。使用天然存在的化合物及其衍生物抗肺炎衣原体的另一种策略被表达。该策略包括使用ChemGPS-NP Chemography工具将基于配体的虚拟筛选应用于502种化合物的天然产物库，然后进行体外衣原体检测。用于二维相似性搜索的参考集由19种已知的植物来源的抗衣原体化合物构成。基于相似性筛选，选择了53个虚拟匹配项进行体外测试。鉴定出导致肺炎衣原体生长抑制≥50％且对宿主细胞活力无影响的六种化合物（前导物）。铅属于全新的抗衣原体化学型，其中之一是霉酚酸（IC 50值0.3μM）。结果表明，使用这种翻转的，与靶标无关的策略有助于促进针对挑战性微生物的抗微生物先导发现。
更新日期：2017-10-18
中文翻译：
基于配体的策略识别特权衣原体天然产物
专心的细胞内病原体肺炎衣原体仍然是抗微生物治疗的困难目标。由于细菌和宿主液泡膜所设置的通透性屏障，以及细菌对持续感染的倾向，治疗失败是常见的。尽管迫切需要新的抗衣原体化合物，但其发现受到技术要求高的测定程序和缺乏经过验证的靶标的挑战。使用天然存在的化合物及其衍生物抗肺炎衣原体的另一种策略被表达。该策略包括使用ChemGPS-NP Chemography工具将基于配体的虚拟筛选应用于502种化合物的天然产物库，然后进行体外衣原体检测。用于二维相似性搜索的参考集由19种已知的植物来源的抗衣原体化合物构成。基于相似性筛选，选择了53个虚拟匹配项进行体外测试。鉴定出导致肺炎衣原体生长抑制≥50％且对宿主细胞活力无影响的六种化合物（前导物）。铅属于全新的抗衣原体化学型，其中之一是霉酚酸（IC 50值0.3μM）。结果表明，使用这种翻转的，与靶标无关的策略有助于促进针对挑战性微生物的抗微生物先导发现。
京公网安备 11010802027423号