Discovery of novel cage-like heterocyclic hybrids as anti-inflammatory agents through the inhibition of nitrite, PGE2 and TNF-α

Bioorg Chem. 2019 Oct:91:103180. doi: 10.1016/j.bioorg.2019.103180. Epub 2019 Aug 3.

Abstract

Novel cage-like indolizine-acenaphthene-pyridinone heterocyclic hybrids were synthesized in good yields through [bmim]Br mediated tandem 1,3-dipolar cycloaddition-annulation sequence. The anti-inflammatory activity of these hybrids was performed using carrageenan-induced hind paw oedema, croton oil-induced ear oedema and cotton pellet-induced granuloma models. Four of these cage-like heterocyclic hybrids viz. 4b, 4d, 4e and 4j showed substantial anti-inflammatory activities against acute and chronic inflammatory models and also showed significant inhibition of PGE2, TNF-α, and nitrite levels in carrageenan-induced hind paw oedema.

Keywords: 1,3-Dipolar cycloaddition; Cage-like heterocyclic hybrids; Inflammation; Ionic liquid; Tumor necrosis factor (TNF-α).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Carrageenan / toxicity
  • Dinoprostone / antagonists & inhibitors*
  • Drug Discovery*
  • Edema / chemically induced
  • Edema / drug therapy*
  • Edema / pathology
  • Granuloma / chemically induced
  • Granuloma / drug therapy*
  • Granuloma / pathology
  • Heterocyclic Compounds / chemistry*
  • Mice
  • Nitrites / antagonists & inhibitors*
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents
  • Heterocyclic Compounds
  • Nitrites
  • Tumor Necrosis Factor-alpha
  • Carrageenan
  • Dinoprostone