185
12
constructed from an iridoid-derived C9 unit and two further carbons supplied from acetate. In Camptotheca acuminata the topoisomerase inhibitor and anticancer agent camptothecin is produced. Rauwolfia species have high levels of reserpine, ajmaline, ajmalicine,
deserpidine, rescinnamine and yohimbine and have therefore been used for the treatment
of several illnesses (hypertension, snakebites, fever, cancer, insanity) in several traditional
medicines. Vinca (periwinkle) is another source of many indole alkaloids, such as vinblastine, vincristine, vindesine and vinorelbine. Catharanthus plants (also periwinkle), contain
at least 70 different alkaloids in their sap; some of those are very similar to Vinca alkaloids,
such as vincristine and vinblastine.
Strictosidine is also the precursor to a group called quinoline alkaloids, which includes
the antimalaria drug quinine (from Cinchona, Rubiacaea). Here the indole core structure
is rearranged into a quinoline system.
When tryptamine is not fused with the terpene group, non-isoprenoid indole alkaloids
are formed. Structurally, serotonin (5-hydroxytryptamine), an important neurotransmitter, also belongs to this chemical group as it is derived from tryptophan. This explains
why several indole alkaloids can bind to serotonin receptors as they have a similar structure. Phytoserotonin has also been identified in several plant species, including legumes,
pineapple, bananas, tomatoes, walnuts and hickory. It acts as a laxative in the intestine of
animals and thus, when fruits of plants are eaten, promotes quick expelling of seeds from
the digestive tract. Serotonin is also found in the spines of stinging nettles, causing the
pain sensation associated with touching these plants.
Phytoserotonin has a similar structure as the plant hormone auxin, and therefore it can
act as auxin inhibitor and is involved in regulating development (Pelagio-Flores et al. 2011).
Other non-isoprenoid indole alkaloids are harmane, harmine and harmaline. They have been
identified in harmal (Peganum harmala) and act as monoamine oxidase inhibitors or induce
tremor in mice (harmaline). The calabar bean (Physostigma venenosum, Fabaceae) contains
physostigmine (also known as eserine), which blocks the degradation of the neurotransmitter acetylcholine by inhibiting the acetylcholine esterase (see 7 Sect. 5.1). Physostigmine is
synthesized by tryptamine methylation, followed by formation of a heterocyclic ring system.
The anti-acetylcholine esterase activity is due to the carbamate side chain rather than the
ring system.
Gramine or donaxine, a methylated tryptophan, has been found in several grasses
(Gramineae, Poaceae) such as Hordeum, Arundo and Phalaris and is toxic for many organisms. Kynurenic acid, another oxidative derivative of tryptophan, can be found in several plants such as dandelion (Taraxacum officinale), common nettle (Urtica dioica) and
potatoes (Solanum tuberosum) and is discussed to inhibit the glutamate and the nicotinic
acetylcholine receptors (Turski et al. 2011; Turski et al. 2012; Zgrajka et al. 2013).
Tryptamine can be methylated to dimethyltryptamine (DMT), a psychedelic drug that
can be extracted from plants such as Mimosa tenuiflora (Fabaceae), Diplopterys cabrerana
(Malpighiaceae) and Psychotria viridis (Rubiaceae) but is also found in toads (Rhinella
marina). Due to its structural similarity with serotonin, it most likely also acts on 5HT 2A -
receptors along with other psychedelics (see 7 Sect. 5.6).
Psychedelic indole alkaloids are also present in fungi. For example, magic mushrooms
(such as Psilocybe) contain derivatives of tryptamine and DMT, such as psilocybin and psilocin (acting on the 5HT 2A -receptor). Several toad species (of the Bufo genus) are known
to contain indole alkaloids, such as bufotenin, a degradation product of psilocybin and
isomer of psilocin. Bufotenin can also be isolated from some Fabaceae and acts on the
5HT 2A receptor. Infection of grass and grains by parasitic fungi of the genus Claviceps
or other filamentous fungi leads to dark dense sclerotia, which harbour ergot alkaloids.
12.2 · Terpenoid Indole Alkaloids
12
constructed from an iridoid-derived C9 unit and two further carbons supplied from acetate. In Camptotheca acuminata the topoisomerase inhibitor and anticancer agent camptothecin is produced. Rauwolfia species have high levels of reserpine, ajmaline, ajmalicine,
deserpidine, rescinnamine and yohimbine and have therefore been used for the treatment
of several illnesses (hypertension, snakebites, fever, cancer, insanity) in several traditional
medicines. Vinca (periwinkle) is another source of many indole alkaloids, such as vinblastine, vincristine, vindesine and vinorelbine. Catharanthus plants (also periwinkle), contain
at least 70 different alkaloids in their sap; some of those are very similar to Vinca alkaloids,
such as vincristine and vinblastine.
Strictosidine is also the precursor to a group called quinoline alkaloids, which includes
the antimalaria drug quinine (from Cinchona, Rubiacaea). Here the indole core structure
is rearranged into a quinoline system.
When tryptamine is not fused with the terpene group, non-isoprenoid indole alkaloids
are formed. Structurally, serotonin (5-hydroxytryptamine), an important neurotransmitter, also belongs to this chemical group as it is derived from tryptophan. This explains
why several indole alkaloids can bind to serotonin receptors as they have a similar structure. Phytoserotonin has also been identified in several plant species, including legumes,
pineapple, bananas, tomatoes, walnuts and hickory. It acts as a laxative in the intestine of
animals and thus, when fruits of plants are eaten, promotes quick expelling of seeds from
the digestive tract. Serotonin is also found in the spines of stinging nettles, causing the
pain sensation associated with touching these plants.
Phytoserotonin has a similar structure as the plant hormone auxin, and therefore it can
act as auxin inhibitor and is involved in regulating development (Pelagio-Flores et al. 2011).
Other non-isoprenoid indole alkaloids are harmane, harmine and harmaline. They have been
identified in harmal (Peganum harmala) and act as monoamine oxidase inhibitors or induce
tremor in mice (harmaline). The calabar bean (Physostigma venenosum, Fabaceae) contains
physostigmine (also known as eserine), which blocks the degradation of the neurotransmitter acetylcholine by inhibiting the acetylcholine esterase (see 7 Sect. 5.1). Physostigmine is
synthesized by tryptamine methylation, followed by formation of a heterocyclic ring system.
The anti-acetylcholine esterase activity is due to the carbamate side chain rather than the
ring system.
Gramine or donaxine, a methylated tryptophan, has been found in several grasses
(Gramineae, Poaceae) such as Hordeum, Arundo and Phalaris and is toxic for many organisms. Kynurenic acid, another oxidative derivative of tryptophan, can be found in several plants such as dandelion (Taraxacum officinale), common nettle (Urtica dioica) and
potatoes (Solanum tuberosum) and is discussed to inhibit the glutamate and the nicotinic
acetylcholine receptors (Turski et al. 2011; Turski et al. 2012; Zgrajka et al. 2013).
Tryptamine can be methylated to dimethyltryptamine (DMT), a psychedelic drug that
can be extracted from plants such as Mimosa tenuiflora (Fabaceae), Diplopterys cabrerana
(Malpighiaceae) and Psychotria viridis (Rubiaceae) but is also found in toads (Rhinella
marina). Due to its structural similarity with serotonin, it most likely also acts on 5HT 2A -
receptors along with other psychedelics (see 7 Sect. 5.6).
Psychedelic indole alkaloids are also present in fungi. For example, magic mushrooms
(such as Psilocybe) contain derivatives of tryptamine and DMT, such as psilocybin and psilocin (acting on the 5HT 2A -receptor). Several toad species (of the Bufo genus) are known
to contain indole alkaloids, such as bufotenin, a degradation product of psilocybin and
isomer of psilocin. Bufotenin can also be isolated from some Fabaceae and acts on the
5HT 2A receptor. Infection of grass and grains by parasitic fungi of the genus Claviceps
or other filamentous fungi leads to dark dense sclerotia, which harbour ergot alkaloids.
12.2 · Terpenoid Indole Alkaloids