Discovery of the inhibitors of tumor necrosis factor alpha with structure-based virtual screening

被引：30

作者：

Choi, Hwanho ^{[1
]}

Lee, Youngseop ^{[2
]}

Park, Hwangseo ^{[1
]}

Oh, Dal-Seok ^{[3
]}

机构：

[1] Sejong Univ, Dept Biosci & Biotechnol, Seoul 143747, South Korea

[2] Diabet Complicat Res Ctr, Div Tradit Korean Med TKM Integrated Res, Korea Inst Oriental Med, Taejon 305811, South Korea

[3] Brain Dis Res Ctr, Korea Inst Oriental Med, Taejon 305811, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 21期

关键词：

Virtual screening; Docking; TNF-alpha; Anti-asthmatic drug; TNF-ALPHA; SEVERE ASTHMA; GENETIC ALGORITHM; SOLVATION; DOCKING; PARAMETERS; UREAS;

D O I：

10.1016/j.bmcl.2010.08.116

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Tumor necrosis factor alpha (TNF-alpha) has been considered as one of the attractive drug targets for allergic diseases including asthma. We have been able to identify five novel TNF-alpha inhibitors with a drug-design protocol involving the structure-based virtual screening and in vitro cell-based assay for antagonistic activity. Because the newly discovered inhibitors are structurally diverse and have the desirable physicochemical properties as a drug candidate, they deserve a further investigation as anti-asthmatic drugs. The interactions of the identified inhibitors in the binding site of TNF-alpha dimer are addressed in detail to understand the mechanisms for the stabilization of the inactive dimeric form of TNF-alpha. (C) 2010 Elsevier Ltd. All rights reserved.

引用

收藏

页码：6195 / 6198

页数：4

相关论文

共 26 条

[1] Relationship of small airway chymase-positive mast cells and lung function in severe asthma [J].

Balzar, S ;

Chu, HW ;

Strand, M ;

Wenzel, S .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2005, 171 (05) :431-439

[2] Development of N-2,4-pyrimidine-N-phenyl-N′-phenyl ureas as inhibitors of tumor necrosis factor alpha (TNF-α) synthesis.: Part 1 [J].

Brugel, Todd A. ;

Maier, Jennifer A. ;

Clark, Michael P. ;

Sabat, Clark Mark ;

Goleblowski, Adam ;

Bookland, Roger G. ;

Laufersweiler, Matthew J. ;

Laughlin, Steven K. ;

VanRens, John C. ;

De, Biswanath ;

Hsieh, Lily C. ;

Mekel, Marlene J. ;

Janusz, Michael J. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (13) :3510-3513

[3] Parameters associated with persistent airflow obstruction in chronic severe asthma [J].

Bumbacea, D ;

Campbell, D ;

Nguyen, L ;

Carr, D ;

Barnes, PJ ;

Robinson, D ;

Chung, KF .

EUROPEAN RESPIRATORY JOURNAL, 2004, 24 (01) :122-128

[4] Novel chromene derivatives as TNF-α inhibitors [J].

Cheng, JF ;

Ishikawa, A ;

Ono, Y ;

Arrhenius, T ;

Nadzan, A .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (21) :3647-3650

[5] New jasmonate analogues as potential anti-inflammatory agents [J].

Dang, Hung The ;

Lee, Hye Ja ;

Yoo, Eun Sook ;

Hong, Jongki ;

Bao, Baoquan ;

Choi, Jae Sue ;

Jung, Jee H. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (24) :10228-10235

[6] ITERATIVE PARTIAL EQUALIZATION OF ORBITAL ELECTRONEGATIVITY - A RAPID ACCESS TO ATOMIC CHARGES [J].

GASTEIGER, J ;

MARSILI, M .

TETRAHEDRON, 1980, 36 (22) :3219-3228

[7]

HAMILTON L, 2003, CLIN EXP ALLERGY, V33, P1

[8] Small-molecule inhibition of TNF-α [J].

He, MM ;

Smith, AS ;

Oslob, JD ;

Flanagan, WM ;

Braisted, AC ;

Whitty, A ;

Cancilla, MT ;

Wang, J ;

Lugovskoy, AA ;

Yoburn, JC ;

Fung, AD ;

Farrington, G ;

Eldredge, JK ;

Day, ES ;

Cruz, LA ;

Cachero, TG ;

Miller, SK ;

Friedman, JE ;

Choong, IC ;

Cunningham, BC .

SCIENCE, 2005, 310 (5750) :1022-1025

[9] Epithelial-mesenchymal interactions in the pathogenesis of asthma [J].

Holgate, ST ;

Davies, DE ;

Lackie, PM ;

Wilson, SJ ;

Puddicombe, SM ;

Lordan, JL .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2000, 105 (02) :193-204

[10] The mechanisms, diagnosis, and management of severe asthma in adults [J].

Holgate, Stephen T. ;

Polosa, Riccardo .

LANCET, 2006, 368 (9537) :780-793