Computational screening and design of traditional Chinese medicine (TCM) to block phosphodiesterase-5
Computational screening and design of traditional Chinese medicine (TCM) to block phosphodiesterase-5
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DOI：
10.1016/j.jmgm.2009.08.004
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发表时间：
2009-10-01
影响因子：
2.9
通讯作者：
Chen, Calvin Yu-Chian
中科院分区：
文献类型：
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作者：
Chen, Calvin Yu-Chian
传统中药淫羊藿、蛇床子和菟丝子自古代汉代（公元前202年-公元220年）起就被用于治疗勃起功能障碍。磷酸二酯酶-5（PDE-5）被认为是治疗勃起功能障碍的靶蛋白。在这项研究中，一个可靠的多元线性回归（MLR）模型（r值= 0.8484）被用来预测新的候选人，这是设计从ES，CM，SC的活动。从对接和药效团分析，ES，CM，SC之间的有效候选人进行了筛选。基于MLR分析和高对接评分，预测SC 01、SC 03和ES 03 b具有高效价。另外，通过分析，我们得出以下结论：（1）疏水性化合物往往是更有效的PDE-5抑制剂：（2）由于大的结合位点，分子量超过500的抑制剂仍然有效;（3）从药效团分析来看，氢键受体的特性是设计新型PDE-5抑制剂的基础;（4）根据MLR分析，环基的数量可以高达6个，但芳环的数量限制在4个才有效。本研究为从中药中筛选PDE-5抑制剂提供了一种新的途径，为进一步确认中药的药理作用提供了科学依据。(C)2009 Elsevier Inc. All rights reserved.
The traditional Chinese medicines (TCM), Epimedium sagittatum (ESs), Cnidium monnieri (CMs), and Semen cuscutae (SCs), were used for treating erectile dysfunction since the ancient Han dynasty (202 BC-AD 220). Phosphodiesterase-5 (PDE-5) is deemed the target protein for inhibition to treat erectile dysfunction. In this study, a reliable multiple linear regression (MLR) model (r value = 0.8484) was used to predict the activities of new candidates which were designed from ES, CM, and SC. From docking and pharmacophore analysis, the potent candidates among ES, CM, and SC were screened. SC01, SC03, and ES03b were predicted to have high potencies based on MLR analysis and high docking scores. Additionally, from our analysis, we make the follow conclusion (1) Hydrophobic compounds tend to be more potent PDE-5 inhibitors; (2) Because of the big binding site, inhibitors with molecular weights over 500 remain potent; (3) From the pharmacophore analysis, the features of hydrogen bond acceptors are the basis for designing novel inhibitors of PDE-5 and (4) According to MLR analysis, the number of ring groups could be up to 6, but the number of aromatic rings was limited to 4 to be potent. This study offers an alternative way to screen PDE-5 inhibitors from TCM and provides a scientific basis for confirming pharmacological actions of TCM. (C) 2009 Elsevier Inc. All rights reserved.