Natural Alkamides: Pharmacology, Chemistry and Distribution

Abstract

Alkamides are a broad and expanding group of bioactive natural compounds found in at least 33 plant families. Despite the relatively simple molecular architecture of alkamides (fig. 1), these natural products show broad structural variability and an important range of biological activities, such as immunomodulatory, antimicrobial, antiviral, larvicidal, insecticidal, diuretic, pungent, analgesic, cannabimimetic and antioxidant activities. Additionally, alkamides are involved in the potentiation of antibiotics and the inhibition of prostaglandin biosynthesis, RNA synthesis and the arachidonic acid metabolism, among others. Many plant species containing alkamides have been used in traditional medicine by different civilizations around the world. Many of the plants containing these natural products have been used in the treatment of toothaches and sore throats (Rios-Chavez et al., 2003). These compounds are present in different organs of the plant, such as roots (Heliopsis longipes, Echinaceae purpurea, Achillea wilhelmsii, Acmella oppositifolia, Asiasarum heterotropoide, Cissampelos glaberrima, etc.), leaves and stems (Aristolochia gehrtii, Phyllanthus fraternus, Amaranthus hypochondriacus, Achyranthes ferruginea, etc.), the pericarpium (Zanthoxylum piperitum and Piper spp.), the placenta of Capsicum spp., the fruits of Piper longum, the flowers of Spilanthes acmella, the seeds of the Piper species and tubers of Lepidium meyenii. It is believed that alkamides act as plant growth regulators, promoting or inhibiting the growth and formation of roots in a dose-dependent manner and showing a positive effect in plant biomass production (Campos-Cuevas, et al., 2008). Structurally, natural alkamides commonly have an aliphatic, cyclic or aromatic amine residue, and a C8 to C18 saturated or unsaturated chain (including double or triple bonds, or both) acid, which can also be aromatic. The nature of the acid (carbon chain lengths, unsaturation level, stereochemistry, etc.) and the amine residues are characteristic of each family and genus of plants such that these characteristics serve as chemotaxonomic criteria (fig. 1). Because the nitrogen atom of alkamides is not part of a heterocyclic ring, these compounds are classified as protoalkaloids or pseudoalkaloids.

Isolation of a novel piperidide from Achillea Moonshine using bioactivity guided fractionation for the treatment of acne

“…Alkamides have mainly been reported in Piperaceae, Asteraceae, Rutaceae and Aristolochiaceae families (Rios, 2012). However, polyacetylenic alkamides have only been found in Asteraceae where they frequently occur in Anthemideae and Heliantheae tribes.…”

“…Most polyacetylenic cyclic amides found in this tribe consist of pyrrolidides and piperidides whereas polyacetylenic piperidides are rare (Bohlman, 1988;Bohlmann et al, 1973;Christensen, 1992;Greger, 1984Greger, , 1988. In this study, the novel antiacne compound identified belongs to the piperidide family, which are known to be antimicrobial, antiviral, larvicidal, insecticidal, diuretic, pungent, analgesic, cannabimimetic and antioxidant (Rios, 2012). Some of the plant sources that are known to have anti-acne effect are Aloe vera (Grace et al, 2008), Azadirachta indica, Curcuma longa, Hemidesmus incidus, Gossypium barbadense (Kanlayavattanakul and Lourith 2011), essential oils of Eucalyptus radiate and Melaleuca alternifolia (Stevensen, 1998).…”

Mass Spectrometry Does Not Need to Be a “Grind”: Plant Secondary Metabolites in Coffee and Black Pepper as a Practical Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Teaching Tool

“…Alkamides are the major bioactive secondary metabolites in Echinacea and Lepidium spp. (Peruvian ginseng), , and these compounds are also responsible for both the pungent or spicy flavors and medicinal properties of chili ( Capsicum spp. ), Szechuan and Japanese pepper ( Zanthoxylum spp.…”

“…), Szechuan and Japanese pepper ( Zanthoxylum spp. ), and black pepper ( Piper nigrum ). − The most abundant alkamides in P. nigrum peppercorns are piperine and piperyline (Figure B), although multiple others have been reported. − Peppercorns are the fruits of the P. nigrum plant and are classified as “black”, “white”, “green”, or “red”, depending on when they are harvested and how they are processed.…”

Jasmonic and Salicylic Acids Enhance Biomass, Total Phenolic Content, and Antioxidant Activity of Adventitious Roots of Acmella radicans (Jacq.) R.K. Jansen Cultured in Shake Flasks

“…The Asteraceae family is among the largest in the Mexican flora, and its ethnobotanical and ethnopharmacological reports have revealed therapeutic use due to its bioactive secondary metabolite diversity [2,3]. Among this plant family, some genera such as Acmella (formerly listed as Spilanthes) [4][5][6] stand out for producing several secondary metabolites, e.g., aliphatic alkamides in roots and flowers, which have analgesic effects on the teeth and throat [7][8][9], while polyphenols have anti-inflammatory, antiseptic, and antioxidant properties [10,11].…”