Total synthesis and in vitro-antifungal activity of (+/-)-2-methoxytetradecanoic Acid

Arch Pharm (Weinheim). 2004 Mar;337(3):152-5. doi: 10.1002/ardp.200300824.

Abstract

The marine fatty acid (+/-)-2-methoxytetradecanoic acid was synthesized in two steps (71% overall yield) starting from commercially available methyl-2-hydroxy-tetradecanoate. The title compound was antifungal against Candida albicans (ATCC 14053) in RPMI medium and Aspergillus niger (ATCC 16404) and Cryptococcus neoformans (ATCC 66031) in SDB medium at the minimum inhibitory concentration (MIC) of 100 mM, which compares to the fungitoxicity of a 2-iodotetradecanoic acid against the same fungi. The title compound was also five to ten times more cytotoxic than capric acid to C. albicans and A. niger in the tested medium but comparable in cytotoxicity to either capric acid and its 2-methoxylated analog to C. neoformans. The antifungal activity of (+/-)-2-methoxytetradecanoic acid is explained in terms of inhibition of N-myristoyltransferase.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyltransferases / antagonists & inhibitors
  • Acyltransferases / biosynthesis
  • Acyltransferases / pharmacokinetics
  • Amphotericin B / pharmacology
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / pharmacology*
  • Aspergillus niger / drug effects
  • Candida albicans / drug effects
  • Cryptococcus neoformans / drug effects
  • Fatty Acids / chemical synthesis
  • In Vitro Techniques
  • Myristates / chemical synthesis*
  • Myristates / pharmacology*
  • Myristic Acids / chemical synthesis*
  • Myristic Acids / pharmacology*

Substances

  • 2-methoxytetradecanoic acid
  • Antifungal Agents
  • Fatty Acids
  • Myristates
  • Myristic Acids
  • Amphotericin B
  • Acyltransferases
  • glycylpeptide N-tetradecanoyltransferase