Moracin M from Morus alba L. is a natural phosphodiesterase-4 inhibitor

被引：59

作者：

Chen, Shang-Ke ^{[2
]}

Zhao, Peng ^{[2
]}

Shao, Yong-Xian ^{[2
]}

Li, Zhe ^{[2
]}

Zhang, Cuixian ^{[1
]}

Liu, Peiqing ^{[2
]}

He, Xixin ^{[1
]}

Luo, Hai-Bin ^{[2
]}

Hu, Xiaopeng ^{[2
]}

机构：

[1] Guangzhou Univ Chinese Med, Coll Chinese Mat Med, Guangzhou 510006, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 09期

关键词：

Moracin M; PDE4; Inhibition; Asthma; Kinetics analysis; Molecular docking; Molecular dynamics simulations; MOLECULAR-DYNAMICS SIMULATIONS; CRYSTAL-STRUCTURES; BINDING; DOCKING; SELECTIVITY; ASTHMA;

D O I：

10.1016/j.bmcl.2012.03.026

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Phosphodiesterase-4 (PDE4) has been identified to be a promising target for treatment of asthma. Moracin M extracted from Chinese herbal drug 'Sang-Bai-Pi' (Morus alba L.) was studied for the inhibitory affinity towards PDE4. It inhibited PDE4D2, PDE4B2, PDE5A1, and PDE9A2 with the IC50 values of 2.9, 4.5, > 40, and > 100 mu M, respectively. Our molecular docking and 8 ns molecular dynamics (MD) simulations demonstrated that moracin M forms three hydrogen bonds with Gln369, Asn321, and Asp318 in the active site and stacks against Phe372. In addition, comparative kinetics analysis of its analog moracin C was carried out to qualitatively validate their inhibitory potency as predicted by the binding free energy calculations after MD simulations. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：3261 / 3264

页数：4

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