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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5454_Библиотеки_им_академика_М_И_Перельмана
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initial evolution of the avonoid pathway thus probably occurred during
colonization of land plants. In contrast to avonols, isoavonoids occur
only sporadically throughout the land plants (
Mann, 2005). Isoavonoids
have been reported in the moss Bryum capillare (Anhut et al., 1984). The
evolution of the avonoid pathway provides an excellent example of how
a biochemically complex trait may be built up in stages, with each addition
being adaptive. Intelligent design through complex biochemical adaptations,
which are irreducibly complex, cannot be resulted by a gradual process
of natural selection. The complex biochemical adaptation is ower color
produced by anthocyanin pigments is through complexity lying in the fact
that anthocyanin production requires at least six sequential biochemical reac
-
tions enabled by six different enzymes. Looking at this character by itself,
there is no question that removal of one enzyme limits the production of
anthocyanins. It is only because the intermediate products that were formed
along the way the diverse avonoids in land plants retained their important
ecological and physiological role and so have not been superseded by other
secondary metabolites. Thus, we are able to recognize that the gradual irre
-
ducible complexity of oral pigment production evolved. The anthocyanin
glycosides of anthocyanidins are primarily responsible for the blue and
violet color of fruits. They are believed to derive from dihydroavonols, but
the nal stage of the biosynthetic origin remains to be elucidated.
The anthocyanins play a vital role as mediators of these interactions. The
variety of hues associated with anthocyanins has increased in the evolutionary
process. Flower color evolution appears to involve loss-of-function muta-
tions in the anthocyanin pathway; it is also well-known that this pathway has
contributed signicantly to the evolution of novel characters. Arguably, the
most important process yielding a new function is gene duplication, followed
by the evolution of a novel functional biomolecule in one of the duplicate
copies (neofunctionalization). An evolutionary analysis of avonoid gene
families suggests that this process has repeatedly given rise to several novel
classes of secondary compounds in plants (Raushur, 2006).
Flower color, in large part, is determined by the oral branches that are
most active in a species. Evolutionary transitions in ower color frequently
are accompanied by which changes in oral morphology that are believed
to enhance the efciency of interactions with new pollinators. “pollinator
syndromes” have been recognized by plant evolutionary biologists for
decades (Faegri & van der Pijl, 1966). For example, bee-pollinated owers
are typically blue-purple, have relatively short, broad tubes, broad limbs
that serve as landing platforms, small amounts of concentrated nectar, and
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The Classes and Biosynthesis of Flavonoids 237
inserted anthers and stigmas. By contrast, hummingbird-pollinated owers
usually have reddish owers, long narrow tubes, small limbs, copious dilute
nectar, and exerted anthers and stigmas. Moth and bat-pollinated owers
tend to be white, fragrant, and open at night. Many evolutionary changes
in ower color thus seem to be the adaptations associated with pollinator
attraction (
Dewick, 1985). Polyphenols and avonoids are double bond
cyclic aromatic groups representing primitive traits like in pteridopsida
and gymnopsida. It also prevails the formation of resins that are saturated
hydrocarbons which can be further broken down and deposited in the older
parts of the plants. If they are soluble, they are categorized as tannins. Antho-
cyanins represent the group of organic compounds which are responsible for
absorbing the UV-radiations. The high amount of avonoids and tannins in
T. cordifolia, along with the large amount of anthocyanins in A. bracteolata,
reect the advancement of the group unisexual, which now is considered
under a separate series Daphnales (Patil et al., 2021).
The development of metabolic pathways that resulted in avonoids would
thus have been beneted to plants that emerged from the primeval oceans.
It is remarkable that the marine plants do not produce avonoids. A shorter
lifetime of the anthocyanins is hardly surprising in view of the shorter life
span of owers when compared to the life cycle of the plant.
Winkel-Shirley
(1999) reported that it is an extensive class of low molecular weight charac
-
terized by the avan nucleus with the presence of characteristic blue, purple,
and red anthocyanin pigments of plant tissues.
Medicinally, avonoids are acting as antiproliferative, antioxidant,
antitumor, anti-cancer, anti-pro apoptotic activities, and anti-inammatory
compounds (Kim et al., 2008). Flavonoids from Vaccinium species exhib-
ited anti-cancer activity (Katsube et al., 2003), protecting the human body
contrary to highly reactive oxygen species (ROS) and endogenous scavenging
compounds (Jadhav et al., 2008; Kerry & Abbey, 1997; Willam et al., 2004).
Flavonoids such as epicatechin are inhibitors of nitrous acid-dependent
nitration and in vitro DNA deamination (
Oldreive et al., 1998).
12.3 CLASSIFICATION OF FLAVONOIDS
Flavonoids are typical phenolic compounds that act as potent antioxidants
and metal chelators. Overall, several of these flavonoids are effective
anticancer promoters and cancer chemopreventive agents. The flavonoids,
ubiquitous in plants, with a common structure of diphenyl propane (C
6
-C
3
-
C
6
), consisting of two aromatic rings linked through three carbons.
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238 Flavonoids as Nutraceuticals
Flavonoids comprise a large group of secondary metabolites which are
derived from subunits supplied by the acetate and shikimate pathways. They
occur exclusively in higher plants and are responsible for much of the avor
of food and the color of owers. A basic C
15
unit is invariably present. It is
established from tracer experiments that the ArC
3
subunit is derived from
Shikimate and that the aromatic Ring A is of polyketide origin (Bhat, 2010;
Keservani & Sharma, 2014).
A urry of research began in an attempt to isolate the various individual
avonoids and to study the mechanism by which avonoids act originated in
1930 when a new substance isolated from oranges, believed to be a member
of a new class of vitamins, as vitamin P. Afterwards it is clear that this
substance was a avonoid (rutin) (
Rice-Evans et al., 1997). Flavonoids are
classied into different groups primarily on the basis of degree of oxidation
of three carbon bridges like anthocyanins, avones, avonols, isoavones,
and avonones. A structural variation in each group is partly due to the
degree and pattern of hydroxylation, methoxylation, or glycosylation.
Flavonoids contain conjugated double bonds and groups (hydroxyl or
other substituents) that can donate electrons through resonance to stabilize the
free radicals, which originate in the electronic spectra of avonoids (Gupta
et al., 2016). Flavonoids are classied into four main groups depending on
the position of the linkage of the aromatic ring to the benzopyrano moiety:
(i) avonoids (2-phenylbenzopyrans) 1; (ii) Isoavonoids (3-benzopyrans)
2; (iii) Neoavonoids (4-benzopyrans) 3 (
Figure 12.2). These groups usually
share a common chalcone precursor and thus genetically and structurally
closely related. Chalcones and Aurones are with C
6
-C
3
-C
6
Backbone named
as minor avonoids. Anthocyanins possess avylium salt structures and are
the glycosides of anthocyanidins. Flavones and isoavones also occur as
hydroxyl derivatives and as glycosides.
FIGURE 12.2 Major groups of flavonoids.
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239 The Classes and Biosynthesis of Flavonoids
12.3.1 FLAVONOIDS
Flavonoids with C
6
-C
3
-C
6
backbone are known as 2-Phenylbenzopyrans.
Based on the degree of oxidation and saturation present in the heterocyclic
C-ring, the flavonoids may be divided into flavan, Flavanone, Flavone,
Flavonol, Flavanonols (Dihydroflavonol), Flavan-3-ol, Flavan-4-ol and
flavan 3,4-diol (Leucoanthocyanidins) (
Figure 12.3).
Flavanones are key intermediates in avonoid chemistry as they can be
converted into avones, isoavone, and Flavanols (Dihydroavonol), avan
3,4-diol (Leucoanthocyanidins) and avan-4-ols. Flavanones contain only
one functional group, kenotic carbonyl at 4-position, and two aromatic rings.
Flavanones are well-known components of Citrus fruits, and they are present
in solid wastes and residues obtained during their industrial processing.
Butrin is a yellow-orange avanone obtained from Butea monosperma
owers used in dying silk and cotton. Myricetin, a yellow-colored dihydro
avonol obtained from Myrica rubra used in tanning, Santal a red-colored
isoavone obtained from Pterocarpus santalinus wood, useful for dying
cotton, wool, leather, and wood. Daidzein, a yellow-colored isoavone from
Glycin max berries used as a food supplement.
Flavones (Keservani et al., 2010a) contain two basic functional groups
carbon-carbon double bond in conjugation with the carbonyl functional
group and the ketonic carbonyl group. Flavone and avonols occurring as
glycosides on hydrolysis yield glucose as rhamnose and a sugar-free aglycon
as anthoxanthidin. The luteolin isolated from Weld (Reseda luteola) leaves
and seed is the oldest yellow dyestuff (avones) used in Europe for dying
silk, wood, and textiles. Some common avones found in owers, leaves,
and seeds of various Primulas, Chrysin in buds of Poplar, Apigenin in yellow
Dahlias (Mann, 2005; Bhat, 2010).
Flavonols are very widely distributed in nature, both in plants and insects.
The yellow dye in the wings of the buttery (Melanargea gelatea), Galangin
in Galanga root, Kampfero in blue Delphinium owers, Quercetin in the
bark of American oak (Overcus tinctoria), Myricetin in myricaceae family
plants, Rutin in Sophora japonica ower. Flavone and avonol with the
basic unit as γ pyrone present as benzo γ pyrone, known as pyrone pigments.
Catechins are colorless crystalline compounds obtained from Catechu
(Harborne, 1982).
Flavonols and avones are not colored. They do absorb strongly in the
UV and, although invisible to the human eye, can be seen by insects. They
often occur at the center of owers and probably acts as “honey guides”
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240 Flavonoids as Nutraceuticals
able to attract insect in their nectars. In return, the insect is accessory in the
process of pollination, carrying away from the ower, not the nectar but also
pollen particles to transfer to other plants (Mann, 2005). They also emitted
as signal substances in order to induce Rhizobia from leguminous roots for
expression of genes required for nodulation (Liu, 2016).
FIGURE 12.3 Some common flavonoids.
12.3.2 ISOFLAVONOIDS
The isoflavonoids are a distinctive subclass of the flavonoids. These
compounds possess a 3-phenyl chroman skeleton biogenetically derived by
1,2-aryl migration in a 2-phenyl chroman precursor. Despite their limited
distribution in the plant kingdom, isoflavonoids are remarkably diverse as
far as structural variations are concerned. Isoflavonoids are subdivided into
the following groups: isoflavones, isoflavone, isoflavone, isoflav-3-ene,
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241 The Classes and Biosynthesis of Flavonoids
isoflavonol, rotenoid, coumestans, 3-arylcoumarin, coumaranochromene,
coumaranochromone, pterocarpon (
Figure 12.4).
FIGURE 12.4 Some common isoflavonoids.
Isoavones are also found in either free or a glycoside. Replacement of
hydrogen atom from C
3
in benzo-γ pyrone ring by phenyl group isoavone,
the rst member of the class isoavone, is formed. Other isoavones are
hydroxyl and methyl or methoxy derivatives are isoavone. The glycosides
on hydrolysis yield sugar-free isoavones. Isoavone, Daidzein, Genistein,
and Irigenin are commonly occurring isoavones, of which Daidzein and
Genistein are found in soybean, Medicarpin (Isoavone) from alfalfa
(Lucerne) is a phytoalexin. Isoavones found in certain forage plants like
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242 Flavonoids as Nutraceuticals
legumes cause infertility in sheep grazing on it has a similar effect on estro-
gens in animals and are thus named phytoestrogens. Genistein (isoavone)
has a strong estrogen effect.
12.3.3 NEOFLAVONOIDS
The neoflavonoids are structurally and biogenetically closely related to the
flavonoids and isoflavonoids, comprise the 4-arylcoumarins (4-aryl-2H-1
-
benzopyran-2-ones), 3,4-dihydro-4-arylcoumarins, and neoflavones (Figure
12.5).
FIGURE 12.5 Neoflavonoids.
12.3.4 MINOR FLAVONOIDS
Natural products such as chalcones and aurones containing C
6
-C
3
-C
6
back-
bone are considered to be minor flavonoids. These groups of compounds
include the 2′-hydroxychalcones, 2′-OH-dihydrochalcones, 2′-OH-retro-
chalcone, aurones (2-benzylidenecoumaranone), and aerosols (Figure 12.6).
The name aurone has been derived from the Latin name ‘Aureus' means
golden, and accordingly, they are golden yellow in color. They possess the
skeleton of 2 benzylidene coumaranone containing ve-membered with
exocyclic carbon-carbon double bond, widely present in fruits and owers
where they play a signicant role in the pigmentation of the part of the plant.
Sulfuretin is a known example of aurone.
Chalcones are related to avonoids in the sense that the pyrin ring is
cleaved in chalcone. The extended conjugation in chalcones is responsible
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243 The Classes and Biosynthesis of Flavonoids
FIGURE 12.6 Minor flavonoids chalcones and aurones.
for their yellow color. As they do not contain a γ pyrone ring and hence
are open-chain avonoids in which two aromatic rings are joined by three
carbon α,β-unsaturated carbonyl system. The corresponding dihydro deriva-
tive is called dihydrochalcone. They generally co-occur with another class
of orange-yellow colored aurones in petals of Asteraceae family owers.
Carthamus tinctorius (safower) is a rare example of isomerization of chal
-
cone to avanones where a yellow pigment in petals (chalcone) and a red
pigment carthamin (avanone) in ower ages.
12.3.5 ANTHOCYANINS
Anthocyanins are glycosides of aglycones. Anthocyanidin occurs in nature
as a special class of flavonoids. Anthocyanins without their sugars are
known as anthocyanidins (Taiz & Zeiger, 2006). Different color of flowers,
fruits, stems, and leaves are due to the presence of anthocyanins and other
co-pigments such as flavones and flavonols responsible for various shades
of blue, purple, mauve, maroon, magenta, and red. Their acidic salts exhibit
red color, metallic (basic) salts show blue color, and neutral display violet
color. There are six major types of anthocyanins with the basic structure of
2 Phenylbenzopyrillum or flavylium widely spread in nature and differ in
their degree of hydroxylation. On hydrolysis, they yield aglycons like pelar-
gonidin, Cyanidin, peonidin, delphinidin, petunidin, malvidin, apigenidin,
luteonidin, and Cynidin (Figure 12.7).
The variegated color of petals almost certainly acts as stimuli for polli-
nating agents. In Ipomoea, blue, and purple-owered species tend to produce
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244 Flavonoids as Nutraceuticals
almost exclusively cyanidin-based anthocyanins. Pathway ux in these
species is almost entirely down the second branch; mutations that knock out
the enzyme F3′H redirect ux down the pelargonidin branch, resulting in red
owers. Red-owered Ipomoea species also almost always produce pelar
-
gonidin-based rather than cyanidin-based anthocyanins (Zufall & Rausher,
2003). In Penstemon (Scrophulariaceae), blue/purple, bee-pollinated owers
FIGURE 12.7 Anthocyanins.
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The Classes and Biosynthesis of Flavonoids 245
tend to produce delphinidin-derived anthocyanins, while red, pollinated by
hummingbird owers tend to produce pelargonidin (Scogin & Freeman,
1987). Adjusting the relative amounts of ux down the different pathway
branches thus seems to be a common way of altering ower color. Thus
natural selection seems to have led to the production of scarlet hues, typical
of pelargonidin or blue of delphinidin, through modication of primitive
pigment cyaniding by loss or gain of hydroxyl group. Anthocyanins appear
at specic developmental stages and may be induced by a number of envi
-
ronmental factors, including visible and UV-B radiation, cold temperature,
and water stress (Linda, 1999;
Nikam, 2007).
12.4 BIOSYNTHESIS OF FLAVONOIDS
From a biogenetic point of view, the C
15
carbon framework of flavonoids
can be divided into two parts, one part consisting of six carbon atoms, which
forms ring A, while the other part consists of nine carbon atoms known as
phenylpropanoid moiety (C
6
-C
3
). These phenyl propanoid moieties also serve
as the precursor of a number of amino acids and phenolic compounds occur
-
ring in nature. It is well established that the biogenesis of ring A proceeds via
the acetate or polyketide route, while that ring B proceeds via the Shikimate
pathway (Bhat et al., 2010).
The majority of avonoids are synthesized by a multifarious metabolic
enzyme situated on the cytoplasmic shell of the endoplasmic reticulum of
plant cells (Burbulis, 1999). Conversely, some avonoids (avonols and
avanols) and a small number of avonoid biosynthesis enzymes further
-
more originate in the nuclei of plant cells (Wang, 2005). This suggests that
avonoids are synthesized in diverse cell compartments in an array to main-
tain particular physiological functions.
The function of Shikimic acid is not restricted to the generation of
amino acids for protein biosynthesis. It also provides a precursor for a large
amount of variety of other substances formed by plants in huge quantities,
particularly phenylpropanoids like avonoids and lignins. The shikimic acid
pathway converts simple carbohydrate precursors (Erythrose 4 Phosphate)
and phosphoenol pyruvate (PEP) to the aromatic ring containing amino
acid phenylalanine, tyrosine, and tryptophan. The most abundant class of
phenolic compounds in plants is derived from deamination of phenylamine
to cinnamic acid by phenylalanine lyase (PAL).
The condensation of PEP and D-erythrose-4-Phosphate was catalyzed by
the 3 deoxy-D-arabino-heptulosonic acid-7-phosphate (DHAP) and inorganic
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