title: 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.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors.forename: Shang-Ke
authors.initials: SK
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Yong-Xian
authors.initials: YX
authors.lastname: Shao
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.forename: Cuixian
authors.initials: C
authors.lastname: Zhang
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
authors.forename: Xixin
authors.initials: X
authors.lastname: He
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Luo
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Hu
mesh_terms: D001572:Benzofurans / Q000494:pharmacology*; D003198:Computer Simulation; D004365:Drugs, Chinese Herbal; D020128:Inhibitory Concentration 50; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D031625:Morus / Q000737:chemistry*; D058988:Phosphodiesterase 4 Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D012118:Resorcinols / Q000494:pharmacology*
chemical_list: D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D058988:Phosphodiesterase 4 Inhibitors; D010936:Plant Extracts; D012118:Resorcinols; C568020:moracin M