Synthesis of the novel (±)-2-methoxy-6-icosynoic acid--a fatty acid that induces death of neuroblastoma cells

Chem Phys Lipids. 2013 Jul-Aug:172-173:14-9. doi: 10.1016/j.chemphyslip.2013.04.004. Epub 2013 May 3.

Abstract

The first total synthesis for the novel fatty acid (±)-2-methoxy-6-icosynoic acid was accomplished in seven steps and in a 14% overall yield starting from 2-(4-bromobutoxy)-tetrahydro-2H-pyran. The title compound displayed an EC50=23±1 μM against the human SH-SY5Y neuroblastoma cell line and an EC50=26±1 μM against the human adenocarcinoma cervix cell line (HeLa) after 48 h of exposure. The corresponding non-methoxylated analog 6-icosynoic acid did not display cytotoxicity (EC50>500 μM) toward the studied cell lines as well as the 2-methoxyicosanoic acid (EC50>300 μM). The critical micelle concentration (CMC=20-30 μM) for the (±)-2-methoxy-6-icosynoic acid was also determined. It was found that α-methoxylation decreases the CMC of a fatty acid.

Keywords: Cancer; Methoxylated fatty acids; Micelles; Neuroblastoma; Synthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Fatty Acids / chemical synthesis*
  • Fatty Acids / chemistry
  • Fatty Acids / toxicity
  • Fatty Acids, Unsaturated / chemical synthesis*
  • Fatty Acids, Unsaturated / chemistry
  • Fatty Acids, Unsaturated / toxicity
  • HeLa Cells
  • Humans
  • Micelles
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Stereoisomerism

Substances

  • 2-methoxy-6-icosynoic acid
  • Fatty Acids
  • Fatty Acids, Unsaturated
  • Micelles