Synthesis of 4-(3-oxo-3-phenylpropyl)morpholin-4-ium chloride analogues and their inhibitory activities of nitric oxide production in lipopolysaccharide-induced BV2 cells

Bioorg Med Chem Lett. 2021 Mar 15:36:127780. doi: 10.1016/j.bmcl.2021.127780. Epub 2021 Jan 8.

Abstract

Based on our previous report that 3-morpholino-1-phenylpropan-1-one 2, one of the fluoxetine's simplified morpholino analogue, inhibited nitric oxide (NO) production, in this paper, various substituted benzene analogues with morpholine hydrochloride of 2 were synthesized and their inhibitory effects on NO production in lipopolysaccharide (LPS)-induced BV2 cells were tested. Among the synthesized compounds, 2-trifluoromethyl analogue 16n (IC50 = 8.6 μM) showed a significantly higher inhibitory activity than that of the parent compound 2a (IC50 > 50 μM) and suppressed NO production dose-dependently without cytotoxicity. Compound 16n also inhibited iNOS expression in LPS-induced BV2 cells at 2, 10 and 20 μM concentrations. These results suggest that compound 16n inhibited NO production by suppressing the expression of iNOS and can be used as a lead structure for developing new inhibitor of NO production.

Keywords: 3-Morpholino-1-phenylpropan-1-one analogues; BV2 cell; NO production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chlorides / chemical synthesis
  • Chlorides / chemistry
  • Chlorides / pharmacology*
  • Dose-Response Relationship, Drug
  • Lipopolysaccharides / antagonists & inhibitors*
  • Lipopolysaccharides / pharmacology
  • Mice
  • Molecular Structure
  • Morpholines / chemical synthesis
  • Morpholines / chemistry
  • Morpholines / pharmacology*
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Structure-Activity Relationship

Substances

  • Chlorides
  • Lipopolysaccharides
  • Morpholines
  • Nitric Oxide