Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10592521 | Bioorganic & Medicinal Chemistry Letters | 2012 | 4 Pages |
Abstract
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 μM, 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.
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Shang-Ke Chen, Peng Zhao, Yong-Xian Shao, Zhe Li, Cuixian Zhang, Peiqing Liu, Xixin He, Hai-Bin Luo, Xiaopeng Hu,