In silico search for multi-target anti-inflammatories in Chinese herbs and formulas
In silico search for multi-target anti-inflammatories in Chinese herbs and formulas
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DOI：
10.1016/j.bmc.2010.01.070
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发表时间：
2010-03-15
影响因子：
3.5
通讯作者：
Hylands, Peter J.
中科院分区：
文献类型：
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作者：
Ehrman, Thomas M.;Barlow, David J.;Hylands, Peter J.
使用药效基团辅助对接，筛选了可能对涉及炎症的四个靶点具有活性的中草药化合物。首先利用蛋白质数据库 (PDB) 中的配体-受体复合物构建多个 LigandScout (LS) 药效团来选择化合物。然后使用 LS 衍生模板对这些化合物进行对接，并根据对接分数进行排序。靶标包括环加氧酶 1 和 2 (COX)、p38 MAP 激酶 (p38)、c-Jun 末端 NH2 激酶 (JNK) 和 4 型 cAMP 特异性磷酸二酯酶 (PDE4)。结果表明，多靶点抑制剂在中药中可能相对常见。除了支持这些结果的实验证据之外，还给出了它们分布的详细信息。介绍了预计对至少三个靶点具有活性的化合物的例子，并概述了它们的特征。还分析了 50 多个草药类别的 192 个中药方剂中含有预测抑制剂的草药分布。在被发现含有大量这些草药的配方中，有传统上用于治疗发烧、头痛、类风湿性关节炎、炎症性肠病、皮肤病、癌症和外伤的配方。讨论了多靶点药物发现与中医药之间的关系。 (C) 2010 Elsevier Ltd. 保留所有权利。
Chinese herbs were screened for compounds which may be active against four targets involved in inflammation, using pharmacophore-assisted docking. Multiple LigandScout (LS) pharmacophores built from ligand-receptor complexes in the protein databank (PDB) were first employed to select compounds. These compounds were then docked using LS-derived templates and ranked according to docking score. The targets comprised cyclo-oxygenases 1 & 2 (COX), p38 MAP kinase (p38), c-Jun terminal-NH2 kinase (JNK) and type 4 cAMP-specific phosphodiesterase (PDE4). The results revealed that multi-target inhibitors are likely to be relatively common in Chinese herbs. Details of their distribution are given, in addition to experimental evidence supporting these results. Examples of compounds predicted to be active against at least three targets are presented, and their features outlined. The distribution of herbs containing predicted inhibitors was also analysed in relation to 192 Chinese formulas from over 50 herbal categories. Among those found to contain a high proportion of these herbs were formulas traditionally used to treat fever, headache, rheumatoid arthritis, inflammatory bowel disorders, skin disease, cancer, and traumatic injury. Relationships between multi-target drug discovery and Chinese medicine are discussed. (C) 2010 Elsevier Ltd. All rights reserved.