Synthesis of novel isoflavone/benzo-δ-sultam hybrids as potential anti-inflammatory drugs

Bioorg Med Chem Lett. 2021 Feb 15:34:127761. doi: 10.1016/j.bmcl.2020.127761. Epub 2020 Dec 24.

Abstract

A small series of novel isoflavone/benzo-δ-sultam hybrids was synthesised and evaluated as potential anti-inflammatory and neuroprotective drugs in LPS-activated BV2 microglia. The benzo-δ-sultam core was constructed in a two-step reaction by coupling 2-halobenzenesulfonamide derivatives with terminal alkynes, followed by a 6-endo-dig cyclisation. The synthesised compounds, including precursors and hybrids, were tested for their ability to inhibit NO and TNF-α production in LPS-stimulated BV2 microglial cells, and the results are promising. The most potent hybrid reduces the NO production to 41%, and the TNF-α to 34% at 20 µM final concentration in the well.

Keywords: Anti-inflammatory; Isoflavone; Microglia; TNF-α; δ-sultam.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Isoflavones / chemistry
  • Isoflavones / pharmacology*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microglia / drug effects*
  • Microglia / metabolism
  • Molecular Structure
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Isoflavones
  • Lipopolysaccharides
  • Sulfonamides
  • Tumor Necrosis Factor-alpha
  • beta-sultam
  • Nitric Oxide