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

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 IC(50) values of 2.9, 4.5, >40, and >100 μM, respectively. Our molecular docking and 8ns 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.

• Authors: Shang-Ke Chen, Peng Zhao, Yong-Xian Shao, Zhe Li, Cuixian Zhang, Peiqing Liu, Xixin He, Hai-Bin Luo, Xiaopeng Hu
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 9 Pg. 3261-4 (May 01 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 22483586 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Benzofurans
• Drugs, Chinese Herbal
• Phosphodiesterase 4 Inhibitors
• Plant Extracts
• Resorcinols
• moracin M

Topics

• Benzofurans (pharmacology)
• Computer Simulation
• Drugs, Chinese Herbal
• Inhibitory Concentration 50
• Kinetics
• Molecular Dynamics Simulation
• Morus (chemistry)
• Phosphodiesterase 4 Inhibitors (chemistry, isolation & purification)
• Plant Extracts (chemistry, pharmacology)
• Protein Binding
• Resorcinols (pharmacology)