Potent In Vitro Antifungal Activities of Naturally Occurring Acetylenic Acids

Li, Xing-Cong; Jacob, Melissa R.; Khan, Shabana I.; Ashfaq, Mohammad; Babu, K. Suresh; Agarwal, Ameeta K.; ElSohly, Hala N.; Manly, Susan P.; Clark, Alice M.

doi:10.1128/aac.01297-07

Cited by 61 publications

(86 citation statements)

References 33 publications

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“…They have been reported to possess a diversity of pharmacological properties, including antibacterial, antifungal, antiparasitic, and antitumor activities (reviewed in references 6 and 44). We have previously described the antifungal properties of 6-acetylenic acids (triple bond at C-6) that were isolated from the plants Pentagonia gigantifolia and Sommera sabiceoides (21,22). Among these, 6-nonadecyonic acid (6-NDA), with a chain length of C 19 (see the structure shown in Fig.…”

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confidence: 99%

A Potent Plant-Derived Antifungal Acetylenic Acid Mediates Its Activity by Interfering with Fatty Acid Homeostasis

Tripathi

Feng

et al. 2012

Antimicrob Agents Chemother

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c 6-Nonadecynoic acid (6-NDA), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogens Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. In the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model yeast Saccharomyces cerevisiae to investigate its mechanism of action. 6-NDA elicited a transcriptome response indicative of fatty acid stress, altering the expression of genes that are required for yeast growth in the presence of oleate. Mutants of S. cerevisiae lacking transcription factors that regulate fatty acid ␤-oxidation showed increased sensitivity to 6-NDA. Fatty acid profile analysis indicated that 6-NDA inhibited the formation of fatty acids longer than 14 carbons in length. In addition, the growth inhibitory effect of 6-NDA was rescued in the presence of exogenously supplied oleate. To investigate the response of a pathogenic fungal species to 6-NDA, transcriptional profiling and biochemical analyses were also conducted in C. albicans. The transcriptional response and fatty acid profile of C. albicans were comparable to those obtained in S. cerevisiae, and the rescue of growth inhibition with exogenous oleate was also observed in C. albicans. In a fluconazole-resistant clinical isolate of C. albicans, a fungicidal effect was produced when fluconazole was combined with 6-NDA. In hyphal growth assays, 6-NDA inhibited the formation of long hyphal filaments in C. albicans. Collectively, our results indicate that the antifungal activity of 6-NDA is mediated by a disruption in fatty acid homeostasis and that 6-NDA has potential utility in the treatment of superficial Candida infections.

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confidence: 99%

A Potent Plant-Derived Antifungal Acetylenic Acid Mediates Its Activity by Interfering with Fatty Acid Homeostasis

Tripathi

Feng

et al. 2012

Antimicrob Agents Chemother

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“…While phytosterols are known to have bioactive prevention properties such as lowering of cholesterol levels [44] and cancer prevention [45] properties. Previous research by Li et al [46] showed that unsaturated fatty acids have antifungal potencies, low toxicities and good pharmaceutical properties.…”

Section: Phytochemistrymentioning

confidence: 99%

Ethnobotanical, phytochemical and pharmacological properties of <i>Crinum bulbispermum</i> (Burm f) Milne-Redh and Schweick (Amaryllidaceae)

Maroyi¹

2016

Trop. J. Pharm Res

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“…Many polyacetylenics have highly potent biological activities, which are used in defence against pathogens and predators 3,12,15 , and some have been investigated as human anti-cancer and anti-microbial treatments 13,16,18,20 . Conjugated polyacetylenic compounds are also very difficult to synthesize chemically; however, we have described a biosynthetic route using soldier beetle genes for heterologous production of these chemicals in yeast using mild conditions.…”

Section: Figure 5 | Phylogenetic Analysis Of Insect Desaturasesmentioning

confidence: 99%

“…The challenging chemistry and variety of potent biological activities of polyacetylenic fatty acids, which includes activities against cancer cells, infecting microbes and plant alleopathy [12][13][14][15][16][17][18][19][20] , have excited interest among natural-product prospectors and bioactive discovery programmes, and have propelled our interest in new molecular structures and biosynthetic origins. In this report, we describe a three-gene pathway isolated from the Australian soldier beetle C. lugubris, leading to an 18-carbon precursor of DHMA, and the first eukaryote biosynthesis of conjugated polyacetylenic compounds.…”

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The convergent evolution of defensive polyacetylenic fatty acid biosynthesis genes in soldier beetles

et al. 2012

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The defensive and bioactive polyacetylenic fatty acid, 8Z-dihydromatricaria acid, is sequestered within a wide range of organisms, including plants, fungi and soldier beetles. The 8Z-dihydromatricaria acid is concentrated in the defence and accessory glands of soldier beetles to repel avian predators and protect eggs. In eukaryotes, acetylenic modifications of fatty acids are catalysed by acetylenases, which are desaturase-like enzymes that act on existing double bonds. Here we obtained acyl Coenzyme A-linked desaturases from soldier beetle RnA and functionally expressed them in yeast. We show that three genes were sufficient for the conversion of a common monounsaturated fatty acid, oleic acid, to the 18 carbon precursor of 8Z-dihydromatricaria acid, that is, 9Z,16Z-octadecadiene-12,14-diynoic acid. These are the first eukaryotic genes reported to produce conjugated polyacetylenic fatty acids. Phylogenetic analysis shows that the genes responsible for 8Z-dihydromatricaria acid synthesis in soldier beetles evolved de novo and independently of the acetylenases of plants and fungi.

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Potent In Vitro Antifungal Activities of Naturally Occurring Acetylenic Acids

Cited by 61 publications

References 33 publications

A Potent Plant-Derived Antifungal Acetylenic Acid Mediates Its Activity by Interfering with Fatty Acid Homeostasis

A Potent Plant-Derived Antifungal Acetylenic Acid Mediates Its Activity by Interfering with Fatty Acid Homeostasis

Ethnobotanical, phytochemical and pharmacological properties of <i>Crinum bulbispermum</i> (Burm f) Milne-Redh and Schweick (Amaryllidaceae)

The convergent evolution of defensive polyacetylenic fatty acid biosynthesis genes in soldier beetles

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