Selective PGHS-2 inhibitors: A rational approach for treatment of the inflammation

被引：24

作者：

Rodrigues, CR

Veloso, MP

Verli, H

Fraga, CAM

Miranda, ALP

Barreiro, EJ

机构：

[1] Univ Fed Rio de Janeiro, Lab Avalicao & Sintese Substancias Bioat, Fac Farm, BR-21944970 Rio De Janeiro, Brazil

[2] Univ Fed Rio de Janeiro, Dept Quim Organ, Inst Quim, BR-21944970 Rio De Janeiro, Brazil

来源：

CURRENT MEDICINAL CHEMISTRY | 2002年 / 9卷 / 08期

关键词：

NSAIDs; PGHS-2; inhibitors; 3D-pharmacophore model; molecular dynamics;

D O I：

10.2174/0929867024606786

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：

Prostaglandin-H synthase exists in two isoforms, PGHS-1 and PGHS-2. PGHS-I is present and is constitutively expressed in most cells and tissues, whereas PGHS-2 is mainly thought to mediate inflammation. Selective prostaglandin-H synthase-2 (or cyclooxygenase-2) inhibitors have been shown to be potent anti inflammatory agents with fewer side effects than currently marketed nonsteroidal anti inflammatory drugs (NSAIDs). This review addresses the main classes of the selective PGHS-2 inhibitors whose selectivity is documented by supporting PGHS-I and PGHS-2 enzyme data. In addition, we also describe our experience in design, synthesis and pharmacological in vivo evaluation of new 1,2-benzodioxole derivatives as candidate of the selective PGHS-2 inhibitors, with special attention to molecular dynamics simulations of these derivatives attached to the active site of PGHS-2.

引用

页码：849 / 867

页数：19

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