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

Abstract

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.

Local Anesthetic Activity from Extracts, Fractions and Pure Compounds from the Roots of Ottonia anisum Spreng. (Piperaceae)

“…Again, exception for piperovatine that has a methoxy as substituent. This chemical pattern is in agreement with those from literature records for N-akylamides from Piper species (Parmar et al 1997, Boonen et al 2012, Greger 2016. Besides, some other amides isolated from the genus Ottonia, such as piperlonguminine, corcovadine and isocorcovadine fit in this profile (Costa and Mors 1981).…”

“…Only pipercallosidine of all three isolated amides could be assayed due to the affordable amount. The characterized metabolites found in O. anisum root extract were in agreement with those from literature data for Piperaceae species (Parmar et al 1997, Ahmad et al 2012, Greger 2016) but just piperovatine and the amide (2E, 4E)-N-isobutyl-9-piperonyl-nona-2,4-dienoic have been described for O. anisum (Giesbrecht et al 1981). Species of the genus Piper and Ottonia have been related as natural sources for alkylamides.…”

“…Those N-alkylamides without an aromatic group in the end of the chain have an uneven number of carbon atoms such as filfiline (n = 22) from P. officinarum. The most common N-moiety groups are isobutyl, n-pentyl, isopentyl, piperidine, pyrrole and pyrrolidine (Parmar et al 1997, Boonen et al 2012, Greger 2016. Considering the amides isolated from O. anisum, here presented, six of them have an acid chain with uneven number of carbon atoms (n = 5, 7 and 9), being five with isobutyl N-moiety (exception for piperine).…”

Mast cell degranulation and calcium influx are inhibited by an Echinacea purpurea extract and the alkylamide dodeca-2E,4E-dienoic acid isobutylamide

“…Although alkylamide suppression of cytokine production has been described previously, the mechanism by which alkylamide-containing medicinal plants mediate their effects remains controversial (Boonen et al, 2012; Greger, 2016). In this report, we evaluated the effects of the alkylamide A15 on mast cell degranulation and calcium influx and found that it inhibited degranulation from RBL-2H3 cells and BMMCs (Figs.…”

Quality evaluation of different varieties of Zanthoxylum bungeanum Maxim. peels based on phenolic profiles, bioactivity, and HPLC fingerprint

“…It is usually used as a characteristic spice with unique tingling taste in the food industry, and is also used to treat toothache, ascariasis, gastralgia, dyspepsia, eczema, and so on, as a traditional Chinese medicine (Ahua et al., 2007; Tewary, Bhardwaj, & Shanker, 2005; Yang, Su, Li, Zhang, & Sun, 2008). In recent years, Z. bungeanum has been considered to be an appealing material for the research of bioactive compounds, including acid amide, volatile oil, alkaloids, and phenolic compounds (Greger, 2016; Wang et al., 2010; Xiong, Shi, & Mizuno, 1995; Yang, Li, Tan, & Jiang, 2013; Zhang et al., 2017). Particularly, the phenolic compounds of Z. bungeanum exhibit outstanding pharmacological activities, such as antioxidant, antibacterial, antitumor, etc.…”