Document Type
Article
Publication Date
2007
Abstract
4-Thiatetradecanoic acid exhibited weak antifungal activities against Candida albicans (ATCC 60193), Cryptococcus neoformans (ATCC 6603 1), and Aspergillus niger (ATCC 16404) (MIC = 4.8-12.7 mM). It has been demonstrated that alpha-methoxylation efficiently blocks P-oxidation and significantly improve the antifungal activities of fatty acids. We examined whether antifungal activity of 4-thiatetradecanoic acid can be improved by a-substitution. The unprecedented (+/-)-2-tiydroxy-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 6603 1), 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-thiatetradecinoic acid was more fungitoxic (MIC = 0.17 mM) than the alpha-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 beta-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.
Recommended Citation
Carballeira, Néstor M, Rosann O'Neill, and Keykavous Parang. "Synthesis And Antifungal Properties Of Alpha-Methoxy And Alpha-Hydroxyl Substituted 4-Thiatetradecanoic Acids." Chemistry And Physics Of Lipids 150.1 (2007): 82-88
DOI:10.1016/j.chemphyslip.2007.06.218
Copyright
Elsevier
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Comments
NOTICE: this is the author’s version of a work that was accepted for publication in Chemistry And Physics Of Lipids. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Chemistry And Physics Of Lipids, volume 150, issue 1, 2007. DOI: 10.1016/j.chemphyslip.2007.06.218
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