Screening of chalcone analogs with anti-depressant, anti-inflammatory, analgesic, and COX-2-inhibiting effects

Bioorg Med Chem Lett. 2020 Jun 1;30(11):127173. doi: 10.1016/j.bmcl.2020.127173. Epub 2020 Apr 6.

Abstract

A group of 2-methyl-4-phenylquinoline-chalcone analogs (2a-2x) was synthesized and investigated for anti-depressant, anti-inflammatory, and analgesic effects as cyclooxygenase-2 inhibitors. Pharmacological experiments identified 24 analogs that exhibited anti-depressant, anti-inflammatory, and analgesic activities. In particular, compounds 2c, 2k, and 2w markedly shortened immobility times and exhibited the most anti-depressant activity. In addition, the mechanisms of action of the analogs 2c, 2k, and 2w were likely related to increased serotonin levels in the central nervous system. Compounds 2c, 2k, and 2w displayed reasonable cyclooxygenase-2 inhibitory effects (IC50 values from 0.21 to 0.29 µmol/L) similar to celecoxib (IC50: 0.19 µmol/L) in vitro. A molecular docking study of compound 2k also was conducted.

Keywords: Analgesic; Anti-depressant; Anti-inflammatory; COX-2-inhibitory; Neurotransmitters; Quinoline-chalcone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemistry*
  • Analgesics / metabolism
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / metabolism
  • Antidepressive Agents / chemistry*
  • Antidepressive Agents / metabolism
  • Binding Sites
  • Celecoxib / chemistry
  • Chalcone / chemistry*
  • Chalcone / metabolism
  • Cyclooxygenase 1 / chemistry
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / chemistry
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / chemistry*
  • Cyclooxygenase 2 Inhibitors / metabolism
  • Drug Design
  • Humans
  • Molecular Docking Simulation
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Antidepressive Agents
  • Cyclooxygenase 2 Inhibitors
  • Chalcone
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Celecoxib