3-Amino-alkylated indoles: unexplored green products acting as anti-inflammatory agents

Future Med Chem. 2020 Jan;12(1):5-17. doi: 10.4155/fmc-2019-0234. Epub 2019 Nov 11.

Abstract

Aim: Over the years, indole has proved to be a versatile scaffold for the design of molecules acting as anti-inflammatory agents. Materials & Methods: A small library of 3-amino-alkylated indoles has been obtained by an optimized Mannich green approach. The anti-inflammatory activity of the new 3-amino-alkylated indoles, GLYC 0-10, was evaluated in RAW 264.7 macrophages. Results: The anti-inflammatory activity of the new 3-amino-alkylated indoles, GLYC 0-10, was evaluatedn and, among them, GLYC 4, 5 and 9 displayed the greatest inhibitory effects on nitric oxide production, with IC50 values of 5.41, 4.22 and 6.3 μM, respectively. Conclusion: Our outcomes, overall, highlight the importance of the indole substitution in the anti-inflammatory activity of these compounds, exerted by acting on the interlinked NF-κB/ERK1/2 pathways.

Keywords: ERK1/2 pathway; Mannich reaction; NF-κB pathway; green chemistry; indoles; inflammation; multicomponent reaction.

MeSH terms

  • Alkylation
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Dose-Response Relationship, Drug
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Molecular Structure
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • RAW 264.7 Cells
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Indoles
  • Lipopolysaccharides
  • NF-kappa B
  • Nitric Oxide
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3