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

被引：63

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

共 23 条

[1]

[Anonymous], 2010, ACC DISC STUD 2 5 5

[2]

[Anonymous], 2005, CHIN PHARM 1, P209

[3] Cyclic nucleotide phosphodiesterases: Molecular regulation to clinical use [J].

Bender, Andrew T. ;

Beavo, Joseph A. .

PHARMACOLOGICAL REVIEWS, 2006, 58 (03) :488-520

[4] Structural basis for the activity of drugs that inhibit phosphodiesterases [J].

Card, GL ;

England, BP ;

Suzuki, Y ;

Fong, D ;

Powell, B ;

Lee, B ;

Luu, C ;

Tabrizizad, M ;

Gillette, S ;

Ibrahim, PN ;

Artis, DR ;

Bollag, G ;

Milburn, MV ;

Kim, SH ;

Schlessinger, J ;

Zhang, KYJ .

STRUCTURE, 2004, 12 (12) :2233-2247

[5]

Case DA., 2008, AMBER 10 University of California

[6] Chemistry of trans-Resveratrol with Singlet Oxygen: [2+2] Addition, [4+2] Addition, and Formation of the Phytoalexin Moracin M [J].

Celaje, Jeff A. ;

Zhang, Dong ;

Guerrero, Angela M. ;

Selke, Matthias .

ORGANIC LETTERS, 2011, 13 (18) :4846-4849

[7] Biochemistry and physiology of cyclic nucleotide Phosphocliesterases: Essential components in cyclic nucleotide signaling [J].

Conti, Marco ;

Beavo, Joseph .

ANNUAL REVIEW OF BIOCHEMISTRY, 2007, 76 :481-511

[8] Protocol for MM/PBSA molecular dynamics simulations of proteins [J].

Fogolari, F ;

Brigo, A ;

Molinari, H .

BIOPHYSICAL JOURNAL, 2003, 85 (01) :159-166

[9] Isoform-selective inhibition of chrysin towards human cytochrome P450 1A2. Kinetics analysis, molecular docking, and molecular dynamics simulations [J].

He, Lin ;

He, Fan ;

Bi, Huichang ;

Li, Jiankang ;

Zeng, Su ;

Luo, Hai-Bin ;

Huang, Min .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (20) :6008-6012

[10] Crystal structure of phosphodiesterase 9 shows orientation variation of inhibitor 3-isobutyl-1-methylxanthine binding [J].

Huai, Q ;

Wang, HC ;

Zhang, W ;

Colman, RW ;

Robinson, H ;

Ke, HM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (26) :9624-9629

← 1 2 3 →