Anxiolytic-Like Action of Selected 4-(Alkylamino)-3-nitrocoumarin Derivatives in BALB/c Mice

Chem Biodivers. 2020 Jun;17(6):e2000206. doi: 10.1002/cbdv.202000206. Epub 2020 Jun 15.

Abstract

In this work, we explored the possible polypharmacological potential of the already established antimicrobials against gastrointestinal pathogens, 4-(alkylamino)-3-nitrocoumarins, as antianxiety agents, using a battery of in vivo experiments. Three chosen coumarin derivatives, differing in the substituent (sec-butylamino, hexadecylamino, or benzylamino) at position 4, at the doses of 25, 50 and 100 mg kg-1 , were evaluated in light/dark, open-field, horizontal wire and diazepam-induced sleep models using male BALB/c mice. Depending on the applied dose, all three tested coumarins displayed a noteworthy anxiolytic-like effect. 4-(sec-Butylamino)-3-nitro-2H-chromen-2-one and 4-(hexadecylamino)-3-nitro-2H-chromen-2-one could be recognized as true anxiolytics in the lowest applied dose, based on three tests, without exerting any sedative effects. Thus, the 3-nitrocoumarin core deserves further chemical diversity exploration in the 'antianxiety' direction.

Keywords: anxiety; coumarin derivatives; light/dark test; open-field test.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / chemistry*
  • Anti-Anxiety Agents / pharmacology
  • Anti-Anxiety Agents / therapeutic use
  • Anxiety / drug therapy
  • Behavior, Animal / drug effects
  • Coumarins / chemistry*
  • Coumarins / pharmacology
  • Coumarins / therapeutic use
  • Diazepam / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Sleep / drug effects

Substances

  • 2H-chromen-2-one
  • Anti-Anxiety Agents
  • Coumarins
  • Diazepam