Highly Unsaturated Isopentyl Amides from Achillea wilhelmsii

In our ongoing study to evaluate the antiprotozoal activity of alkamides from Asteraceae, a dichloromethane extract from the roots of Anacyclus pyrethrum L. showed a moderate in vitro activity against the NF54 strain of Plasmodium falciparum and against Leishmania donovani (amastigotes, MHOM/ET/67/L82 strain). Seven pure alkamides and a mixture of two further alkamides were isolated by column chromatography followed by preparative high performance liquid chromatography. The alkamides were identified by mass- and NMR-spectroscopic methods as tetradeca-2E,4E-dien-8,10-diynoic acid isobutylamide (anacycline, 1), deca-2E,4E-dienoic acid isobutylamide (pellitorine, 2), deca-2E,4E,9-trienoic acid isobutylamide (3), deca-2E,4E-dienoic acid 2-phenylethylamide (4), undeca-2E,4E-dien-8,10-diynoic acid isopentylamide (5), tetradeca-2E,4E,12Z-trien-8,10-diynoic acid isobutylamide (6), and dodeca-2E,4E-dien acid 4-hydroxy-2-phenylethylamide (7). Two compounds—undeca-2E,4E-dien-8,10-diynoic acid 2-phenylethylamide (8) and deca-2E,4E-dienoic acid 4-hydroxy-2-phenylethylamide (9)—were isolated as an inseparable mixture (1:4). Compounds 3, 4, and 5 were isolated from Anacyclus pyrethrum L. for the first time. While compounds 4 and 5 were previously known from the genus Achillea, compound 3 is a new natural product, to the best of our knowledge. All isolated alkamides were tested in vitro for antiprotozoal activity against Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani and for cytotoxicity against L6 rat skeletal myoblasts.

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“…All analytical data were in full agreement with literature data: compounds 1 , 5 , 6 [ 11 ], 2 , 8 [ 12 ], 4 [ 13 ], 7 , 9 [ 15 ].…”

Section: Methodssupporting

confidence: 84%

“…A further compound with a molecular mass of 272 amu ([M + H] + at m / z 272.2025) was identified as deca-2E,4E-dienoic acid 2-phenylethylamide ( 4 ) by its 1 H-spectrum ( Figure S8 ) in comparison with literature [ 13 ]. The compound was known from Achillea wilhelmsii but is now described as a constituent of A. pyrethrum for the first time.…”

Section: Resultsmentioning

confidence: 91%

Alkamides from Anacyclus pyrethrum L. and Their in Vitro Antiprotozoal Activity

et al. 2017

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“…With regard to the enormous capacity for vegetative reproduction and gregarious clonal growth due to the abundant formation of rootsuckers in many Achillea species, e.g. in A. wilhelmsii, the accumulation of alkamides in these parts deserves also ecological attention (Greger and Hofer 1987). Taking into account that unsaturated alkamides were considered to be unstable when heated and to be non-volatile with water vapour it is noteworthy that the three piperideides 101e, 105e, 106e together with 101a and 101b were detected after distillation in a GC/MS analyses of the root oil of A. distans ssp.…”

Section: Phytochem Revmentioning

confidence: 99%

Alkamides: a critical reconsideration of a multifunctional class of unsaturated fatty acid amides

Greger

2015

Phytochem Rev

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Alkamides are natural products formed by connecting straight-chain, mostly unsaturated, aliphatic acids with various amines by an amide linkage. More than 300 derivatives are known from eight plant families consisting of various combinations of 200 acids with 23 amines. Apart from a few saturated derivatives alkamides with unsaturated acid parts are grouped into compounds with purely olefinic patterns and those with olefinic and acetylenic linkages. Derived from C 18 oleic acid the acid parts are modified either by chain elongations to C 28 or by oxidative shortenings to C 4 acid residues. Substrate and regiospecific desaturases and acetylenases are responsible for their characteristic patterns of unsaturation. Amine parts are derived from various amino acids by decarboxylation. Beside the widespread isobutylamines alkamides with six-and five-membered ring amines and those with phenylalanine derived amines are characteristic for the Asteraceae and Piperaceae while benzylamines are restricted to the Brassicaceae. Within the Asteraceae 2-methylbutylamine distinguishes the tribe Heliantheae from Anthemideae characterized by ring amines. Alkamides with elongated olefinic acid parts are mainly found in Piperaceae and Brassicaceae while acetylenic acid parts are typical for Asteraceae. A wide variety of biological activities ranges from the characteristic pungent/ tingling property and high insecticidal toxicity to significant antifungal, antibacterial, antiprotozoal, molluscicidal, cercaricidal, and acaricidal activity. They also act as plant growth-promoting substances. Position and stereochemistry of the double bonds are essential for the different qualities of the pungent taste. Medically alkamides possess anti-inflammatory and analgesic properties and are responsible for immunomodulatory and cannabinomimetic effects.

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“…The biogenetic characteristic isopentylamides (IPAs) were only described in Achillea (e.g. 123) (Greger and Hofer, 1987), while the N-methyl IBA (e.g. 79) are found in the Anthemideae tribe (Anacyclus pyrethrum) (Jente et al, 1972) as well as in the Rutaceae family, encompassing Clauseneae tribe (Riemer et al, 1997) and Zanthoxyleae tribe (Adesina et al, 1997;Adesina and Reisch, 1989;Cheng et al, 2004).…”

Section: Q10mentioning

confidence: 99%

“…Most straight chain fatty acids derive from nonaromatic acyl precursor, like oleic (18:1), linoleic (18:2) and linolenic (18:3) fatty acids (Greger and Hofer, 1987;Greger et al, 1983;Martin and Becker, 1985). Successive dehydrogenations and dehydrations, frequently accompanied by isomerization, lead to characteristic alkenyc and alkynic structures (Greger, 1984), while different oxidative processes contribute to chain shortening or epoxide structures (Christensen and Lam, 1991a;Greger, 1984;Greger et al, 1983Martin and Becker, 1985).…”

Section: Biosynthesismentioning

confidence: 99%

Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides

Boonen

Bronselaer

Nielandt

et al. 2012

Journal of Ethnopharmacology

133

109

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a b s t r a c tEthnopharmacological relevance: N-Alkylamides (NAAs) are a promising group of bioactive compounds, which are anticipated to act as important lead compounds for plant protection and biocidal products, functional food, cosmeceuticals and drugs in the next decennia. These molecules, currently found in more than 25 plant families and with a wide structural diversity, exert a variety of biologicalpharmacological effects and are of high ethnopharmacological importance. However, information is scattered in literature, with different, often unstandardized, pharmacological methodologies being used. Therefore, a comprehensive NAA database (acronym: Alkamid) was constructed to collect the available structural and functional NAA data, linked to their occurrence in plants (family, tribe, species, genus). Materials and methods: For loading information in the database, literature data was gathered over the period 1950-2010, by using several search engines. In order to represent the collected information about NAAs, the plants in which they occur and the functionalities for which they have been examined, a relational database is constructed and implemented on a MySQL back-end. Results: The database is supported by describing the NAA plant-, functional-and chemical-space. The chemical space includes a NAA classification, according to their fatty acid and amine structures. Conclusions: The Alkamid database (publicly available on the website http://alkamid.ugent.be/) is not only a central information point, but can also function as a useful tool to prioritize the NAA Q8 choice in the evaluation of their functionality, to perform data mining leading to quantitative structure-property relationships (QSPRs), functionality comparisons, clustering, plant biochemistry and taxonomic evaluations.

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Highly Unsaturated Isopentyl Amides from Achillea wilhelmsii

Cited by 13 publications

References 19 publications

Alkamides from Anacyclus pyrethrum L. and Their in Vitro Antiprotozoal Activity

Alkamides from Anacyclus pyrethrum L. and Their in Vitro Antiprotozoal Activity

Alkamides: a critical reconsideration of a multifunctional class of unsaturated fatty acid amides

Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides

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