Synthesis and biological evaluation of longanlactone analogues as neurotrophic agents

Bioorg Med Chem Lett. 2018 Feb 15;28(4):673-676. doi: 10.1016/j.bmcl.2018.01.020. Epub 2018 Jan 12.

Abstract

Longanlactone analogues were synthesized using a route featuring Friedel-Crafts acylation, Sonogashira coupling and 1,3-dipolar cycloaddition reactions. Structure-activity relationships were investigated for neurotrophic activity. Compound 6 was found to have the most potent neurotrophic activity among all the synthesized analogues in Neuro2a cells as evidenced by a battery of in vitro/cell based assays for assessment of neurogenic and potential neurotrophic activity including neurite outgrowth assay and real time PCR for popular markers of augmented neurotrophic activity. Compound 6 might serve as a template for further development of highly effective neurotrophic molecules.

Keywords: Longanlactone; Neurotrophic agent; Pyrrole alkaloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Cell Line, Tumor
  • Drug Design
  • Lactones / chemical synthesis
  • Lactones / pharmacology*
  • Lactones / toxicity
  • Mice
  • Molecular Structure
  • Neuronal Outgrowth / drug effects*
  • Pyrroles / chemical synthesis
  • Pyrroles / pharmacology*
  • Pyrroles / toxicity
  • RNA, Messenger / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Lactones
  • Pyrroles
  • RNA, Messenger