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 μM), and against Cryptococcus neoformans ATCC 66031 (MIC<5.7 μM). 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 μM. 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 μM) against the fluconazole-resistant C, albicans ATCC 14053 strain, but it showed a MIC value of only 100 μM against C. albicans ATCC 60193. 2,6-Hexadecadiynoic acid and 2-hexadecynoic acid also displayed a MIC of 140–145 μM 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.
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Abbreviations
- AMB:
-
amphotericin B
- FLC:
-
fluconazole
- LORA:
-
low oxygen recovery assay
- MABA:
-
microplate alamar blue assay
- MIC:
-
minimum inhibitory concentration
- NCCLS:
-
National Committee for Clinical Laboratory Standards
- SDA:
-
Sabouraud dextrose agar
- SDB:
-
Sabourand dextrose broth
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Carballeira, N.M., Sanabria, D., Cruz, C. et al. 2,6-hexadecadiynoic acid and 2,6-nonadecadiynoic acid: Novel synthesized acetylenic fatty acids as potent antifungal agents. Lipids 41, 507–511 (2006). https://doi.org/10.1007/s11745-006-5124-4
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DOI: https://doi.org/10.1007/s11745-006-5124-4