Selective PGHS-2 inhibitors: a rational approach for treatment of the inflammation.
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.
Rodrigues
C R
CR
Laboratorio de Avaliacao e Sintese de Substancias Bioativas, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, PO Box 68006, Rio de Janeiro, 21944-970, Brazil.
Veloso
M P
MP
Verli
H
H
Fraga
C A M
CA
Miranda
A L P
AL
Barreiro
E J
EJ
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011451:Prostaglandin-Endoperoxide Synthases; D013329:Structure-Activity Relationship
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases