Structural basis for selective inhibition of COX-2 by nimesulide

被引：34

作者：

Fabiola, GF

Pattabhi, V ^{[2
]}

Nagarajan, K

机构：

[1] Recon Ltd, Bangalore 560076, Karnataka, India

[2] Univ Madras, Dept Crystallog & Biophys, Madras 600025, Tamil Nadu, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1998年 / 6卷 / 12期

关键词：

NSAIDS; selective inhibition of COX-2; computer modelling; nimesulide;

D O I：

10.1016/S0968-0896(98)80012-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nimesulide 1 is a novel nonsteroidal antiinflammatory drug which inhibits the enzyme cyclooxygenase 2 (COX-2) more selectively than cyclooxygenase 1 (COX-1). Molecular modelling studies have been carried out on complexes of 1 with COX-1 and with mutants of COX-1 simulating COX-2. These indicate that the mutations I523V and S516A largely contribute to the selectivity. A comparative study with SC-558 2 has also been performed. (C) 1998 Elsevier Science Ltd. All rights reserved.

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收藏

页码：2337 / 2344

页数：8

相关论文

共 18 条

[1]

BERNETT A, 1993, DRUGS S, V46, P1

[2]

DEWITT DL, 1990, J BIOL CHEM, V265, P5192

[3] NIMESULIDE [J].

DUPONT, L ;

PIROTTE, B ;

MASEREEL, B ;

DELARGE, J ;

GECZY, J .

ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS, 1995, 51 (pt 3) :507-509

[4] NS-398, A NEW ANTIINFLAMMATORY AGENT, SELECTIVELY INHIBITS PROSTAGLANDIN-G/H SYNTHASE CYCLOOXYGENASE (COX-2) ACTIVITY IN-VITRO [J].

FUTAKI, N ;

TAKAHASHI, S ;

YOKOYAMA, M ;

ARAI, I ;

HIGUCHI, S ;

OTOMO, S .

PROSTAGLANDINS, 1994, 47 (01) :55-59

[5] A single amino acid difference between cyclooxygenase-1 (COX-1) and -2 (COX-2) reverses the selectivity of COX-2 specific inhibitors [J].

Gierse, JK ;

McDonald, JJ ;

Hauser, SD ;

Rangwala, SH ;

Koboldt, CM ;

Seibert, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (26) :15810-15814

[6] Prostaglandin synthase 2 [J].

Herschman, HR .

BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1996, 1299 (01) :125-140

[7] Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents [J].

Kurumbail, RG ;

Stevens, AM ;

Gierse, JK ;

McDonald, JJ ;

Stegeman, RA ;

Pak, JY ;

Gildehaus, D ;

Miyashiro, JM ;

Penning, TD ;

Seibert, K ;

Isakson, PC ;

Stallings, WC .

NATURE, 1996, 384 (6610) :644-648

[8] Synthesis and use of iodinated nonsteroidal antiinflammatory drug analogs as crystallographic probes of the prostaglandin H-2 synthase cyclooxygenase active site [J].

Loll, PJ ;

Picot, D ;

Ekabo, O ;

Garavito, RM .

BIOCHEMISTRY, 1996, 35 (23) :7330-7340

[9] THE STRUCTURAL BASIS OF ASPIRIN ACTIVITY INFERRED FROM THE CRYSTAL-STRUCTURE OF INACTIVATED PROSTAGLANDIN H-2 SYNTHASE [J].

LOLL, PJ ;

PICOT, D ;

GARAVITO, RM .

NATURE STRUCTURAL BIOLOGY, 1995, 2 (08) :637-643

[10] Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2 [J].

Luong, C ;

Miller, A ;

Barnett, J ;

Chow, J ;

Ramesha, C ;

Browner, MF .

NATURE STRUCTURAL BIOLOGY, 1996, 3 (11) :927-933