2,6-hexadecadiynoic Acid and 2,6-nonadecadiynoic Acid: Novel Synthesized Acetylenic Fatty Acids as Potent Antifungal Agents

Lipids. 2006 May;41(5):507-11. doi: 10.1007/s11745-006-5124-4.

Abstract

The hitherto unknown 2,6-hexadecadiynoic acid, 2,6-nonadecadiynoic acid, and 2,9-hexadecadiynoic acid were synthesized in two steps and in 11-18% overall yields starting from either 1,5-hexadiyne or 1,8-nonadiyne. Among all the compounds 2,6-hexadecadiynoic acid displayed the best overall antifungal activity against both the fluconazole-resistant Candida albicans strains ATCC 14053 and ATCC 60193, with a minimum inhibitory concentration (MIC of 11 microM), and against Cryptococcus neoformans ATCC 66031 (MIC < 5.7 microM). 2,9-Hexadecadiynoic acid did not display any significant cytotoxicity against the fluconazole-resistant C. albicans strains, but it showed fungitoxicity against C. neoformans ATCC 66031 with a MIC value of < 5.8 microM. Other FA, such as 2-hexadecynoic acid, 5-hexadecynoic acid, 9-hexadecynoic acid, and 6-nonadecynoic acid were also synthesized and their antifungal activities compared with those of the novel acetylenic FA. 2-Hexadecynoic acid, a known antifungal FA, exhibited the best antifungal activity (MIC = 9.4 microM) against the fluconazole-resistant C. albicans ATCC 14053 strain, but it showed a MIC value of only 100 microM against C. albicans ATCC 60193. 2,6-Hexadecadiynoic acid and 2-hexadecynoic acid also displayed a MIC of 140-145 microM toward Mycobacterium tuberculosis H37Rv in Middlebrook 7H12 medium. In conclusion, 2,6-hexadecadiynoic acid exhibited the best fungitoxicity profile compared with other analogues. This diynoic FA has the potential to be further evaluated for use in topical antifungal formulations.

Publication types

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

MeSH terms

  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Candida albicans / drug effects
  • Fatty Acids / chemical synthesis*
  • Fatty Acids / chemistry
  • Fatty Acids / pharmacology
  • Fatty Acids, Unsaturated / chemical synthesis*
  • Fatty Acids, Unsaturated / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • 2,6-hexadecadiynoic acid
  • 2,6-nonadecadiynoic acid
  • Antifungal Agents
  • Fatty Acids
  • Fatty Acids, Unsaturated