Synthesis and antifungal properties of α-methoxy and α-hydroxyl substituted 4-thiatetradecanoic acids

Néstor M. Carballeira, Rosann O'Neill, Keykavous Parang

Research output: Contribution to journalArticlepeer-review

Abstract

4-Thiatetradecanoic acid exhibited weak antifungal activities against Candida albicans (ATCC 60193), Cryptococcus neoformans (ATCC 66031), and Aspergillus niger (ATCC 16404) (MIC = 4.8-12.7 mM). It has been demonstrated that α-methoxylation efficiently blocks β-oxidation and significantly improve the antifungal activities of fatty acids. We examined whether antifungal activity of 4-thiatetradecanoic acid can be improved by α-substitution. The unprecedented (±)-2-hydroxy-4-thiatetradecanoic acid was synthesized in four steps (20% overall yield), while the (±)-2-methoxy-4-thiatetradecanoic acid was synthesized in five steps (14% overall yield) starting from 1-decanethiol. The key step in the synthesis was the hydrolysis of a trimethylsilyloxynitrile. In general, the novel (±)-2-methoxy-4-thiatetradecanoic acid displayed significantly higher antifungal activities against C. albicans (ATCC 60193), C. neoformans (ATCC 66031), and A. niger (ATCC 16404) (MIC = 0.8-1.2 mM), when compared with 4-thiatetradecanoic acid. In the case of C. neoformans the (±)-2-hydroxy-4-thiatetradecanoic acid was more fungitoxic (MIC = 0.17 mM) than the α-methoxylated analog, but not as effective against A. niger (MIC = 5.5 mM). The enhanced fungitoxicity of the (±)-2-methoxy-4-thiatetradecanoic acid, as compared to decylthiopropionic acid, might be the result of a longer half-life in the cells due to a blocked β-oxidation pathway which results in more time to exert its toxic effects. Thus, these novel fatty acids may have applications as probes to study fatty acid metabolic routes in human cells.

Original languageEnglish (US)
Pages (from-to)82-88
Number of pages7
JournalChemistry and Physics of Lipids
Volume150
Issue number1
DOIs
StatePublished - Nov 2007
Externally publishedYes

Keywords

  • Antifungal
  • Decylthiopropionic acid
  • Methoxylated fatty acids
  • Synthesis
  • Thia fatty acids

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

Fingerprint Dive into the research topics of 'Synthesis and antifungal properties of α-methoxy and α-hydroxyl substituted 4-thiatetradecanoic acids'. Together they form a unique fingerprint.

Cite this