Moracin M from Morus alba L. is a natural phosphodiesterase-4 inhibitor
Moracin M from Morus alba L. is a natural phosphodiesterase-4 inhibitor
复制标题
来自 Morus alba L. 的 Moracin M 是一种天然磷酸二酯酶 4 抑制剂
DOI：
10.1016/j.bmcl.2012.03.026
复制
发表时间：
2012-05-01
影响因子：
2.7
通讯作者：
Hu, Xiaopeng
中科院分区：
文献类型：
--
作者：
Chen, Shang-Ke;Zhao, Peng;Hu, Xiaopeng
磷酸二酯酶-4(PDE4)已被认为是治疗哮喘的有前途的靶点。从中草药桑白皮(Morus alba L.)对其对PDE4的抑制亲和力进行了研究。对PDE4D2、PDE4B2、PDE5A1和PDE9A2的IC50值分别为2.9、4.5、40和100 mU M。我们的分子对接和8 ns分子动力学(MD)模拟表明，莫拉星M与活性中心的Gln369、Asn321和Asp318形成三个氢键，并与Phe372形成堆叠。此外，对其类似物莫拉星C进行了比较动力学分析，定性地验证了分子动力学模拟后结合自由能计算所预测的抑制效力。(C)2012爱思唯尔有限公司。保留所有权利。
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.