Pd-N-heterocyclic carbene catalyzed synthesis of piperidine alkene-alkaloids and their anti-cancer evaluation

Bioorg Med Chem Lett. 2014 Feb 15;24(4):1180-3. doi: 10.1016/j.bmcl.2013.12.108. Epub 2014 Jan 3.

Abstract

A facile synthesis of piperidine alkene-alkaloids including natural (+)-Caulophyllumine B in high yields has been developed by Heck cross-coupling reaction catalyzed by simple in situ formed palladium-N-heterocyclic carbenes (Pd-NHCs). Formation of Pd(0) nanoparticles has been noticed during the reaction course. The synthesized piperidine alkene-alkaloids were evaluated for in vitro anti-cancer activity against a panel of human tumor cell lines of lung, breast and ovarian. Several of these piperidine alkene-alkaloids were found to possess highest growth inhibition activity than the standard drug cisplatin and support the concept to modulate drug receptor interaction.

Keywords: Anti-cancer activity; Heck coupling; N-Heterocyclic carbene; Natural products; Piperidine alkene–alkaloids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry*
  • Alkenes / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Catalysis
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Heterocyclic Compounds / chemistry
  • Humans
  • MCF-7 Cells
  • Methane / analogs & derivatives
  • Methane / chemistry
  • Molecular Conformation
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry*
  • Palladium / chemistry
  • Piperidines / chemistry*
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Alkenes
  • Antineoplastic Agents
  • Heterocyclic Compounds
  • Organometallic Compounds
  • Piperidines
  • carbene
  • Palladium
  • piperidine
  • Methane