Selective PGHS-2 Inhibitors: A Rational Approach for Treatment of theInflammation

Title: Selective PGHS-2 Inhibitors: A Rational Approach for Treatment of theInflammation

Volume: 9 Issue: 8

Author(s): C. R. Rodrigues, M. P. Veloso, H. Verli, C. A.M. Fraga, A. L.P. Miranda and E. J. Barreiro

Affiliation:

Keywords: nsaids, pghs-2 inhibitors, 3d-pharmacophore model, molecular dynamics, acety isalicylic acid, diclofenac, sulindac, indomethacin, piroxicam, selective pghs-2 inhibitors, 1,2-diarylcyclopentenes

Abstract: Prostaglandin-H synthase exists in two isoforms, PGHS-1 and PGHS-2. PGHS-1 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 antiinflammatory agents with fewer side effects than currently marketed nonsteroidal antiinflammatory drugs (NSAIDs). This review addresses the main classes of the selective PGHS-2 inhibitors whose selectivity is documented by supporting PGHS-1 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.

Cite this article as:

Rodrigues R. C., Veloso P. M., Verli H., Fraga A.M. C., Miranda L.P. A. and Barreiro J. E., Selective PGHS-2 Inhibitors: A Rational Approach for Treatment of theInflammation, Current Medicinal Chemistry 2002; 9 (8) . https://dx.doi.org/10.2174/0929867024606786