Design and synthesis of dual active neovibsanin derivatives based on a chemical structure merging method

Bioorg Med Chem Lett. 2020 Oct 15;30(20):127497. doi: 10.1016/j.bmcl.2020.127497. Epub 2020 Aug 12.

Abstract

A hybrid compound consisting of neovibsanin and trans-banglene was designed according to a structure merging method and synthesized via a sequence of key steps including a Diels-Alder cycloaddition, stereoselective alkynylation, and intramolecular oxa-Michael addition reaction. The biological activity of the synthetized acetal compound and its hemiacetal analogue was investigated in PC12 cells. These studies revealed that the designed hybrid compounds displayed neuritogenic activity. Furthermore, a relatively strong neurite outgrowth promoting activity was observed in the presence of NGF. These results suggest that the designed hybrid compound exhibited a dual activity.

Keywords: Neovibsanin; Neurite-outgrowth promoting activity; Neuritogenic activity; Phenylbutadiene dimer; Structure merging method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diterpenes / chemical synthesis
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Molecular Structure
  • Neurites / drug effects*
  • Neurites / metabolism
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Rats
  • Structure-Activity Relationship

Substances

  • Diterpenes
  • Neuroprotective Agents
  • neovibsanin A