The chemical synthesis and preliminary biological studies of phosphodiester and phosphorothioate analogues of 2-methoxy-lysophosphatidylethanolamine

Bioorg Med Chem Lett. 2016 Aug 1;26(15):3725-9. doi: 10.1016/j.bmcl.2016.05.075. Epub 2016 May 27.

Abstract

The chemical synthesis of phosphorothioate/phosphodiester analogues of 2-methoxy-lysophosphatidylethanolamine has been described. For the preparation of phosphorothioate derivatives oxathiaphospholane approach has been employed. The phosphodiester compounds were prepared by OXONE® oxidation of corresponding phosphorothioates. Each lysophospholipid analogue was synthesized as a series of four compounds, bearing different fatty acid residues both saturated (14:0, 16:0, 18:0) and unsaturated (18:1). The methylation of glycerol 2-hydroxyl function was applied in order to increase the stability of prepared analogues by preventing 1→2 acyl migration. The cytotoxicity of newly synthesized 2-methoxy-lysophosphatidylethanolamine derivatives was evaluated with resazurin-based method in prostate cancer PC3 cell line. The highest reduction of cell viability was noted for LPE analogues containing myristoyl acyl chain.

Keywords: 2-Methoxy-LPE derivatives; Cytotoxicity; Lysophosphatidylethanolamine analogues; Phosphodiesters; Phosphorothioates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Esters / chemical synthesis
  • Esters / chemistry
  • Esters / pharmacology*
  • Humans
  • Lysophospholipids / chemistry
  • Lysophospholipids / pharmacology*
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / chemical synthesis
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacology*

Substances

  • 2-methoxy-lysophosphatidylethanolamine
  • Esters
  • Lysophospholipids
  • Sulfhydryl Compounds