210
13
fennel, celery and parsley) and ivy derives from the crepenynate pathway (Dawid et al.
2015) (. Fig. 13.2). Falcarinol has been made responsible for the bitter taste and alleged
allergenic, antibacterial, antimycobacterial and antifungal activities of these herbs and vegetables. Furthermore, falcarinol shows significant binding interactions with both cannabinoid receptors (Leonti et al. 2010). Also panaxydol and panaxynol, found in ginger (Panax
ginseng, Araliaceae), are derived from the crepenynate pathway. They have been attributed
cytotoxic activity against several human tumour cells. Cicutoxin is a C 17 - polyacetylene
from water hemlocks (Cicuta sp., Apiaceae), and a related compound is oenanthotoxin
from Oenanthe crocata (Apiaceae). Cicutoxin acts as noncompetitive antagonists of the
GABA A receptor by binding to the picrotoxin binding site within the chloride channel to
block ion flow through the channel (Berger et al. 2018).
13.3.2 N-Acylethanolamines
N-acylethanolamines are fatty acid derivatives found in many eukaryotes. Several
variations can be distinguished, N-arachidonoylethanolamine (AEA, anandamide),
N- palmitoylethanolamine and N-oleoylethanolamine. In animals, they are generated from membrane phospholipids through hydrolysis or by sequential deacylation
of N- arachidonoyl phosphatidylethanolamine or similar structures. Anandamide is
one of the endogenous ligands of the cannabinoid receptor (therefore called endocannabinoid), whereas the other N-acylethanolamines are receptor-inactive (Felder et al.
1993). Only recently, the presence of N-acylethanolamines in plants has been demonstrated, but it is not clear if the biosynthesis is similar to synthesis of these compounds
in animals. In contrast to animals, plants probably do not generally produce arachidonic
acid, therefore plants do not produce anandamides and only N-acylethanolamines that
do not interact with CB receptors (. Fig. 13.2). Nevertheless, N-acylethanolamines (e.g.
N- linoleoylethanolamide, N-oleoylethanolamide and N-palmitoylethanolamide) have
been shown to inhibit the enzyme fatty acid amid hydrolase (FAAH), which inhibits
anandamide breakdown and thus leads to an increase in endocannabinoid levels (Coulon
et al. 2012a, b); see . Fig. 5.7b. N-Acylethanolamines are highest in seeds of various plant
species, such as Medicago truncatula (Kilaru et al. 2007) and the cacao tree (Theobroma
cacao, Malvaceae) and decrease upon germination. They also seem to interact in plants
with abscisic acid (ABA) signalling pathways (Teaster et al. 2007; Keereetaweep et al.
2013; Blancaflor et al. 2014).
13.3.3 Alkylamides, N-acyl amides (e.g. Capsaicin)
Alkylamides comprise about 200 chemically related compounds and are amines acylated
with a variety of different unsaturated fatty acid. Usually, they have an aliphatic, cyclic
or aromatic amine residue and a C8 to C18 saturated or unsaturated chain (including
double or triple bonds or both), which can also be aromatic. As the nitrogen atom of
alkamides is not part of a heterocyclic ring, these compounds are classified as pseudo
alkaloids. There structure resembles animal endocannabinoids such as anandamide;
therefore, alkamides are highly active in the central nervous system. Plants belonging to
the Asteraceae, Convolvulaceae, Euphorbiaceae, Menispermaceae and Rutaceae families
specialize in the biosynthesis of alkamides with both amine and acid aliphatic residues.
Chapter 13 · Minor Groups of Secondary Metabolites
13
fennel, celery and parsley) and ivy derives from the crepenynate pathway (Dawid et al.
2015) (. Fig. 13.2). Falcarinol has been made responsible for the bitter taste and alleged
allergenic, antibacterial, antimycobacterial and antifungal activities of these herbs and vegetables. Furthermore, falcarinol shows significant binding interactions with both cannabinoid receptors (Leonti et al. 2010). Also panaxydol and panaxynol, found in ginger (Panax
ginseng, Araliaceae), are derived from the crepenynate pathway. They have been attributed
cytotoxic activity against several human tumour cells. Cicutoxin is a C 17 - polyacetylene
from water hemlocks (Cicuta sp., Apiaceae), and a related compound is oenanthotoxin
from Oenanthe crocata (Apiaceae). Cicutoxin acts as noncompetitive antagonists of the
GABA A receptor by binding to the picrotoxin binding site within the chloride channel to
block ion flow through the channel (Berger et al. 2018).
13.3.2 N-Acylethanolamines
N-acylethanolamines are fatty acid derivatives found in many eukaryotes. Several
variations can be distinguished, N-arachidonoylethanolamine (AEA, anandamide),
N- palmitoylethanolamine and N-oleoylethanolamine. In animals, they are generated from membrane phospholipids through hydrolysis or by sequential deacylation
of N- arachidonoyl phosphatidylethanolamine or similar structures. Anandamide is
one of the endogenous ligands of the cannabinoid receptor (therefore called endocannabinoid), whereas the other N-acylethanolamines are receptor-inactive (Felder et al.
1993). Only recently, the presence of N-acylethanolamines in plants has been demonstrated, but it is not clear if the biosynthesis is similar to synthesis of these compounds
in animals. In contrast to animals, plants probably do not generally produce arachidonic
acid, therefore plants do not produce anandamides and only N-acylethanolamines that
do not interact with CB receptors (. Fig. 13.2). Nevertheless, N-acylethanolamines (e.g.
N- linoleoylethanolamide, N-oleoylethanolamide and N-palmitoylethanolamide) have
been shown to inhibit the enzyme fatty acid amid hydrolase (FAAH), which inhibits
anandamide breakdown and thus leads to an increase in endocannabinoid levels (Coulon
et al. 2012a, b); see . Fig. 5.7b. N-Acylethanolamines are highest in seeds of various plant
species, such as Medicago truncatula (Kilaru et al. 2007) and the cacao tree (Theobroma
cacao, Malvaceae) and decrease upon germination. They also seem to interact in plants
with abscisic acid (ABA) signalling pathways (Teaster et al. 2007; Keereetaweep et al.
2013; Blancaflor et al. 2014).
13.3.3 Alkylamides, N-acyl amides (e.g. Capsaicin)
Alkylamides comprise about 200 chemically related compounds and are amines acylated
with a variety of different unsaturated fatty acid. Usually, they have an aliphatic, cyclic
or aromatic amine residue and a C8 to C18 saturated or unsaturated chain (including
double or triple bonds or both), which can also be aromatic. As the nitrogen atom of
alkamides is not part of a heterocyclic ring, these compounds are classified as pseudo
alkaloids. There structure resembles animal endocannabinoids such as anandamide;
therefore, alkamides are highly active in the central nervous system. Plants belonging to
the Asteraceae, Convolvulaceae, Euphorbiaceae, Menispermaceae and Rutaceae families
specialize in the biosynthesis of alkamides with both amine and acid aliphatic residues.
Chapter 13 · Minor Groups of Secondary Metabolites