New substituted pyrazole derivatives targeting COXs as potential safe anti-inflammatory agents

Future Med Chem. 2019 Aug;11(15):1871-1882. doi: 10.4155/fmc-2018-0548.

Abstract

Aim: Everyday studies prove the increasing need for newer and safer agents to control cellular inflammatory response, an underlying cause for the pathophysiology of many other clinical cases. Results: Two newly designed sets of schiff 5a-h and chlacone 6a-f substituted pyrazoles were synthesized and evaluated for their in vivo/vitro anti-inflammatory activities. Most potent representatives were chosen for investigation of ulcerogenic and molecular docking properties. Conclusion: The synthesized compounds showed considerable edema inhibition percentage range if compared with celecoxib (13-93% and 58-93%, respectively) at different time intervals. Compound 6e showed the best screening results if compared with celecoxib (inhibition % = 93.62 and 93.51% at 5 h, COX-1/COX-2 selectivity index SI = 215.44 and 308.16 and ulcer index = 7.25 and 8, respectively).

Keywords: NSAID; acetophenone; anti-inflammatory; celecoxib; chalcones; cyclooxygenase; docking; pyrazole; schiff; ulcer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / therapeutic use
  • Binding Sites
  • Catalytic Domain
  • Celecoxib / pharmacology
  • Celecoxib / therapeutic use
  • Cyclooxygenase 1 / chemistry*
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / chemistry*
  • Cyclooxygenase 2 / metabolism
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / veterinary
  • Hydrogen Bonding
  • Male
  • Molecular Docking Simulation
  • Pyrazoles / chemistry*
  • Pyrazoles / metabolism
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents
  • Pyrazoles
  • pyrazole
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Celecoxib