Insect Antifeedant Potential of Xanthohumol, Isoxanthohumol, and Their Derivatives

Article abstract of DOI:10.1021/acs.jafc.5b02025

Xanthohumol (14) and isoxanthohumol (6) derived from hop (Humulus lupulus L., Cannabaceae) and selected chalcone and chromene derivatives, obtained by chemical synthesis, were studied for antifeedant activity against the peach-potato aphid (Myzus persicae [Sulz.]). The study used also commercially available 4-chromanone (1), flavanone (4), naringenin (5), chromone (7), flavone (8), 7-aminoflavone (9), trans-chalcone (10), and 4-methoxychalcone (12). For chromone derivatives it was observed that the presence of a phenyl substituent at C-2 in the chromone (7) skeleton increased the insect antifeedant activity, and this activity was observed for a longer time. Also, the introduction of an amino group at C-7 of flavone (8) considerably increased the insect antifeedant activity, which was observed for the whole test time. Among the compounds examined, the strongest deterrents were isoxanthohumol (6), 7-methoxy-2,2-dimethylchroman-4-one (3), 7-aminoflavone (9), and 4-ethyl-4′-methoxychalcone (13).

Full text of DOI:10.1021/acs.jafc.5b02025

Article
pubs.acs.org/JAFC
Insect Antifeedant Potential of Xanthohumol, Isoxanthohumol, and
Their Derivatives
,
†
§
§
and Mirosław Anioł†
Monika Stompor,* Katarzyna Dancewicz, Beata Gabrys,
†
́
Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland
§
́ ́
Department of Botany and Ecology, University of Zielona Gora, Szafrana 1, 65-516 Zielona Gora, Poland
ABSTRACT: Xanthohumol (14) and isoxanthohumol (6) derived from hop (Humulus lupulus L., Cannabaceae) and selected
chalcone and chromene derivatives, obtained by chemical synthesis, were studied for antifeedant activity against the peach-potato
aphid (Myzus persicae [Sulz.]). The study used also commercially available 4-chromanone (1), flavanone (4), naringenin (5),
chromone (7), flavone (8), 7-aminoflavone (9), trans-chalcone (10), and 4-methoxychalcone (12). For chromone derivatives it
was observed that the presence of a phenyl substituent at C-2 in the chromone (7) skeleton increased the insect antifeedant
activity, and this activity was observed for a longer time. Also, the introduction of an amino group at C-7 of flavone (8)
considerably increased the insect antifeedant activity, which was observed for the whole test time. Among the compounds
examined, the strongest deterrents were isoxanthohumol (6), 7-methoxy-2,2-dimethylchroman-4-one (3), 7-aminoflavone (9),
and 4-ethyl-4′-methoxychalcone (13).
KEYWORDS: antifeedants, chalcones, isoxanthohumol, xanthohumol, M. persicae (Sulz.)
INTRODUCTION
There are also studies on the chemical synthesis of the
precursors of natural flavonoids, chalcones, and other flavonoid
derivatives, so as to find how different structure modifications
affect their pharmacological activity (cytotoxic, anti-inflamma-
tory, anticancer, antimalarial, and antifeedant (feeding
■
Phenolic compounds are widely distributed in plants, where
they play roles of natural coloring agents, antioxidants,
insecticides, and fungicides. Most flavonoids contain a 2-
1
phenylchromane skeleton. The group of flavonoids comprises
also chalcones. 2′-Hydroxychalcones and their dihydro
derivatives without the heterocyclic C-ring play an essential
role in the biosynthesis of all classes of flavonoid
25−27
deterrent)).
Because of the health risks from the widespread use of
pesticides and artificial fertilizers, there has been an increasing
interest in alternative, safer, and more environmentally friendly
plant protection agents. As an alternative to toxic pesticides and
for environmental reasons, the compounds with pesticidal
activity that are naturally found in plants are more often used
2
−4
compounds.
Common hop Humulus lupulus L. (Cannaba5-
ceae) contains over 1000 various chemical substances.
Flavonoids found in hop (H. lupulus L.) are under careful
investigation, due to their pro-health properties.
6
−9
28
nowadays in agriculture. Not only do these substances
destroy unwanted microflora and other pests, they are also safe
for humans and the environment, which is the most important
issue. Being natural compounds they are fully biodegradable;
moreover, they are active toward a specific group of insects.
Therefore, they are considered environmentally friendly. They
may act on the taste receptors of insects and cause them to stop
feeding on plants, which leads to starvation and death,
eventually.
Xanthohumol (14), the most important chalcone found in
hop cones at about 1%, has many valuable biological properties.
Apart from a strong antioxidant activity, it demonstrated
antiviral and antimicrobial and anti-inflammatory proper-
ties. Additionally, it was confirmed that xanthohumol (14)
inhibits in vitro new blood vessel formation in the carcino-
genesis process and has antiproliferative activity against
different cancer cell lines, such as human breast cancer
1
0
11
(
MCF-6, MCF-7, T47-D), human colon cancer (HT-29),
12−16
Because of the small amount of bioactive compounds in plant
material, the extraction and use of natural compounds for insect
control on a wide scale is costly. For this reason, there is a
strong demand for synthetic behavior-modifying chemicals that
are simple to obtain in the laboratory. At the same time, certain
modifications of natural compound molecules may increase the
human ovarian carcinoma (A-2780), and prostate cancer.
There are several literature papers concerning the other two
hop flavonoids of great interest, isoxanthohumol (6) and 8-
prenylnaringenin, the content of which in hop cones is from 10
17
to 100 times lower than of xanthohumol. Their metabolism in
18−20
microbial cells and mammals was also studied.
A very
29−32
potency of their deterrent activity.
In the present work we
promising tool for medical diagnostics may be haptens
were interested in whether the incorporation of the prenyl,
methyl, hydroxyl, phenyl, and amino groups would affect the
containing a hop flavonoid skeleton, which can be employed
21
for the production of monoclonal antibodies. Due to the fact
that the only natural source of hop flavonoids and phenolic
2
2,23
acids in the human diet is beer,
recently there have been
Received: April 23, 2015
Revised: July 14, 2015
Accepted: July 15, 2015
Published: July 15, 2015
research efforts to achieve chemical and biological stand-
ardization of the hop extract to maintain constant composition
of hop-based preparations, potential therapeutic agents.
24
©
2015 American Chemical Society
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biological activity. Altogether, three natural compounds,
xanthohumol (14), isoxanthohumol (6), and naringenin (5),
and 11 synthetic derivatives with various structural modifica-
tions were examined for aphid-deterrent activity.
behavior of the peach-potato aphid (M. persicae [Sulz.]) was
evaluated. We investigated also the effect of structural
modifications of these flavonoid molecules on aphid behavior.
We selected compounds of diverse chemical structures,
belonging to three flavonoid groups, compounds with 4-
chromanone (1), chromone (7), or trans-chalcone (10)
skeletons.
Usually, antifeedants are natural compounds with a lactone
2
9−31
32,33
ring,
but they may also belong to terpenes
or phenolic
3
4
compounds. Many plants have strong repellent properties,
and for this reason they have been used for a long time to repel
the wheat weevil, the major pest of stored cereal grains. This
group of plants includes field mint (Mentha arvensis), common
yarrow (Achillea millefolium), and several other common plant
species. Obtained by extraction, preparations of lavender
Lavandula luisieri) and rough cocklebur (Xanthium sibiricum)
demonstrated insecticidal activity, among others, against the
MATERIALS AND METHODS
■
Reagents. Chemical reagents were purchased from Sigma-Aldrich,
Merck, Chempur, and Alfa Aesar. For the study we used commercially
available 4-chromanone (1) (Sigma-Aldrich), flavanone (4) (Alfa
Aesar), naringenin (5), chromone (7) (Sigma-Aldrich), flavone (8)
3
5
(
(
Sigma-Aldrich), 7-aminoflavone (9) (Sigma-Aldrich), trans-chalcone
36,37
(10) (Sigma-Aldrich), and 4-methoxychalcone (12) (Sigma-Aldrich).
General Procedures. The structures of products obtained were
determined by spectroscopic methods ( H NMR, C NMR, IR, and
HR ESI-MS). The purity of compounds 2, 3, 11, and 13 was
established by gas chromatography (GC) using an HP-5 capillary
column, whereas, for compounds 6 and 14, high-performance liquid
chromatography (HPLC) was employed, with the help of the
peach-potato aphid (Myzus persicae).
very rich source of antifeedants. Among them, Indian neem
Azadirachta indica) is one of the best known, because it
Tropical plants are a
1
13
(
contains the strongest of known feeding repellents, azadir-
achtin. Nawrot et al. in 2013 proved the strong deterrent
activity of ionic liquids toward wheat weevil beetles (Sitophilus
granarius L.), confused flour beetle larvae (Tribolium confusum
19
reversed-phase C-18 column as described perviously. For the
biological tests we used the compounds with the purity >95%.
Synthesis of Compounds. 7-Hydroxy-2,2-dimethylchroman-4-
one (2) was obtained in the reaction of 1,3-dihydroxybenzene with
dimethylacrylic acid (DMAA) in the presence of zinc chloride in
phosphorus oxychloride, followed by isomerization of the intermediate
38
Duv.), and khapra beetle larvae (Trogoderma granarium Ev.).
This activity was equal to or stronger than that of azadirachtin.
There is increasing application of microbial agents, so-called
bioinsecticides, that contain live bacterial cultures, mostly of the
39
genus Bacillus (Bacillus thuringiensis). Another large group of
47
product according to a modified method of Alizadeh et al. (80% of
biopreparations that inhibit plant pest development is based on
isolated yield). The spectroscopic data were consistent with those
40
47,48
viruses and nematodes. Apart from interacting with insect
chemoreceptors of taste, preparations of antifeeding activity
may inhibit the fertility of insects, prolong their larval
reported in the literature.
In the next step the purified product (2)
was subjected to the Williamson ether synthesis with methyl iodide to
give 7-methoxy-2,2-dimethylchroman-4-one (3), the spectroscopic
4
9
41,42
data of which matched those reported by An et al. The synthesis of
development, or inhibit the transmission of some viruses.
4
-hydroxychalcone (11) and 4-ethyl-4′-methoxychalcone (13) was
According to literature data, biological methods constitute
only a small fraction of plant protection management. One
reason is that there have been no effective biological methods
of crop protection developed, especially concerning control of
diseases and pests of cereals and plants of the families Fabaceae
and Brassicaceae, which are essential for the production of
50
carried out according to the literature method under strongly basic
conditions (KOH), using methanol as a solvent. Xanthohumol (14)
51
was isolated using the earlier described method from spent hops, the
residue of supercritical carbon dioxide hop extraction, which was
delivered by the Supercritical Extraction Department of the New
Chemical Syntheses Institute in Puławy, Poland. The second
prenylated hop flavonoid, isoxanthohumol (6), was obtained by the
alkaline isomerization of xanthohumol (14) according to the method
4
3
organic food. Go
̈
kc ȩ et al. in 2011 proved antifeedant activity
of the extract from hop cones (H. lupulus) against the Colorado
potato beetle (Leptinotarsa decemlineata).
5
2
44
of Wilhelm and Wessjohann.
Cultures of Aphids and Plants. Aphids (M. persicae) and plants
Chinese cabbage Brassica pekinensis) were reared in the laboratory at
In our previously published study, we found that one of the
hop extracts examined significantly deterred M. persicae settling
on treated leaves, and the effect was relatively stable and lasted
(
2
0 °C, 65% realtive humidity, and a 16/8 h light/dark photoperiod. All
experiments were carried out under the same conditions.
4
5
at least 24 h. However, aphid probing and phloem sap
consumption were not impeded. Therefore, we hypothesized
that the extract contained a component that could reach sieve
elements using the symplastic or apoplastic pathway and
produce a delayed, postingestional metabolic detrrent effect
without evoking the rejection behavior based on gustatory
stimuli. Consequently, we decided that there was a need for a
more detailed study to find which components of the hop
extract were responsible for the deterrent activity. Exogenously
applied hop chemicals, α- and β-hop acids and colupulone, had
an antifeedant effect on the grain aphid (Sitobion avenae) and
bird cherry-oat aphid Rhopalosiphum padi. However, to the
best of our knowledge, there is no information about the
deterrent activity of hop flavonoids toward plant pests,
especially aphids. There is also no study on the antifeedant
activity of chalcone (10) and its structural analogues toward the
peach-potato aphid (M. persicae).
Aphid Settling. This bioassay allows aphid host preferences to be
studied under seminatural conditions. In this bioassay, aphids are given
free choice between control and treated leaves. The standard leaf-dip
5
3
method was applied for the evaluation of activities of xanthohumol
14), isoxanthohumol (6), and their derivatives. The compounds
(
studied were applied by immersing a leaf in 0.1% ethanolic solution of
a given compound for 30 s. Control leaves of similar size were
immersed in 70% ethanol, which was used as a solvent for the tested
compounds. Treated and control leaves were placed in a Petri dish and
allowed to air-dry for 1 h before being offered to the insects. Next,
aphids were placed in the dish along the line that divided the area into
two halves so that aphids could choose between treated (on half of a
Petri dish) and control leaves (on the other half of the dish). Aphids
that settled, that is, they did not move and the position of their
antennae indicated feeding, on each leaf were counted at 1, 2, and 24 h
intervals after access to the leaf (8 replicates, 20 viviparous apterous
females/replicate). Aphids that were moving or out of any of the leaves
were not counted.
46
The data were analyzed using one-way ANOVA (Statistica 6.1.
package). If aphids showed a clear preference for the leaves treated
with the tested compound (P < 0.05), the compound was described as
having attractant properties. If aphids settled mainly on the control
The aim of our research was to evaluate the deterrent activity
of natural flavonoid compounds found in hop (H. lupulus):
xanthohumol (14) and isoxanthohumol (6). The settling
6
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a
Table 1. Deterrent Activity of Selected Derivatives of 4-Chromanone (1) to the Peach-Potato Aphid M. persicae (Sulz.)
a
Numbers for T, test, and C, control, represent mean number of aphids settled on test or control leaves (choice test); p, significance level
(
ANOVA); significant differences (Student’s t test, p < 0.05) between number of aphids settled on either half of the Petri dish are in bold; DI, indices
of deterrence.
half of the Petri dish (p < 0.05), the compound tested in the respective
choice test was labeled a deterrent. From the data thus obtained the
indices of deterrence (DI) were calculated (DI , DI , and DI
24
corresponding with 1, 2, and 24 h after exposure monitoring,
respectively):
properties toward the peach-potato aphid. In comparison,
xanthohumol (14) did not demonstrate such an activity. In
contrast, xanthohumol (14) was a weak attractant. However,
strong deterrent properties of isoxanthohumol (6) were
expressed with a delay, that is, at least 2 h after treatment
1
2
DI = (C − T/C + T)
(
DI24 = 0.6, p = 0.0000) (Tables 1 and 3).
The compounds with strongly polar groups in the aromatic
C is the number of aphids settled on control leaves, and T is the
number of aphids settled on the leaves treated with the tested
compound. The value of DI ranged between 1 (ideal deterrent) and
ring, such as hydroxyl ones, were inactive, as opposed to their
methoxy derivatives with a 4-chromanone skeleton (2 and 3)
and to chalcones (11 and 12).
−1 (ideal attractant).
Comparing the activity of ketones (7) and (1), we observed
RESULTS AND DISCUSSION
that hydrogenation of the C −C double bond in compound 7
■
2
3
Aphid Settling. On the basis of the bioassay, we found that
the natural hop flavanone, isoxanthohumol (6), has deterrent
resulted in a switch from attractant to deterrent activity.
However, the effect on aphid behavior was of various potencies
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a
Table 2. Deterrent Activity of Selected Derivatives of Chromone (7) to the Peach-Potato Aphid M. persicae (Sulz.)
a
Numbers for T, test, and C, control, represent mean number of aphids settled on test or control leaves (choice test); p, significance level
ANOVA); significant differences (Student’s t test, p < 0.05) between number of aphids settled on either half of the Petri dish are in bold; DI, indices
(
of deterrence.
and durabilities. For 4-chromanone (1), strong deterrent
activity was noted until the second hour of the experiment,
whereas chromone (7) proved to be a weak attractant to the
peach-potato aphid. The opposite situation was observed for
the derivatives with a phenyl substituent at C-2, where flavone
Differences in the durability of deterrent effects of
compounds examined in the present study, for example,
isoxanthohumol (6), and changes in their activity over time
may be caused by changing conditions of their action.
Presumably, it may be related to altered concentration of a
tested substance in the phloem juice and changes in the pH,
(
8) (DI = 0.5, p = 0.0006) was more active than flavanone (4),
1
45
arising from metabolic transformations in a plant. Addition-
ally, aphids may decompose some substances with the help of
their saliva enzymes. The important factors may be also aphid
endogenous enzymes and symbiotic microbes, which can
which proved to be inactive: the relative index of deterrence
was within the range from DI = 0.2 (p = 0.1597) to DI = DI
1
2
24
=
0.3 (p = 0.0383 and p = 0.0922, respectively (Tables 1 and 2).
In the case of the derivatives with a chromone system, the
presence of a phenyl group at C-2 resulted in an increase in the
deterrent activity; during the initial 2 h after treatment later on,
54
perform detoxification of tested compounds. Xanthohumol
14), the most important hop prenylated chalcone, in the in
(
vitro study was transformed into isoxanthohumol (6) and 8-
the deterrent effect ceased (flavone (8): DI = 0.5, p = 0.0006;
1
55
prenylnaringenin. Biotransformations of isoxanthohumol (6)
DI = 0.4, p = 0.0090; DI = 0.4, p = 0.0609). The introduction
2
24
56
57
using human liver cells and fungi led to the product of O-
demethylation, 8-prenylnaringenin, which is the strongest
phytoestrogen known so far. An aphid attack may induce
synthesis of some organic compounds in B. pekinensis as a
defense response to feeding. In response to the oxidative stress
caused by aphids, a plant may activate a very efficient
production of certain enzymes (for example, antioxidative
ones, such as superoxide dismutase or catalase), hormones, and
signaling molecules, which are part of plant defense against
of an amine group at C-7 in the flavanone led to a considerable
increase of the antifeedant activity, which was observed during
the whole time of the experiment. The relative coefficient of
deterrence values from DI = 0.7 after 1 h (p = 0.0002) to DI =
0.5 after 24 h (p = 0.0167) determined for compound 9 proved
its high deterrent properties (Table 2).
It was observed that in the case of chalcone derivatives, the
compound that caused the strongest reduction of aphid settling
on treated leaves was 4-methoxychalcone (12). It was proved
58
invading insect herbivores (e.g., H O and NO). These may
2
2
by the values of the relative coefficient of deterrence (DI = 0.5,
1
also cause transformations of tested compounds into their
p = 0.0086; DI = 0.5, p = 0.0386). However, the effect of 4-
59
2
derivatives.
methoxychalcone (12) on inhibition of aphid settling was
short-lived. 4′-Methoxy-4-ethylchalcone (13) proved to be also
an active deterrent, which additionally reduced aphid settling
during the whole experiment time (Table 3). The relative index
Structure−Activity Aspects. The current state of the art
in antifeedant activity of flavonoid compounds relates to plant
extracts, pure compounds, products of their metabolism, and
60,61
62
also their synthetic analogues.
Russel et al. came to the
of deterrence value (DI) was within the range from DI = 0.25
conclusion that the lack of substituents in ring C of flavanone as
1
to DI24 = 0.30 at p < 0.05. The deterrent activity at 2 h after
well as the lack of 3-oxo groups (−OH, −OCH ) at C-3 led to
3
application was also observed for trans-chalcone (10) (DI =
an increase in antifeeding activity of the compounds toward
2
0.3, p = 0.0406; DI24 = 0.4, p = 0.0216) (Table 3).
larvae of Ctenopsteustis obliquana, which feed on avocado leaf
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a
Table 3. Deterrent Activity of Selected Derivatives of Chalcone (10) to the Peach-Potato Aphid M. persicae (Sulz.)
a
Numbers for T, test and C, control, represent mean number of aphids settled on test or control leaves (choice test); p, significance level (ANOVA);
significant differences (Student’s t test, p < 0.05) between number of aphids settled on either half of the Petri dish are in bold; DI, indices of
deterrence.
shoots and young fruitlets. It is an advantage for antifeedant
activity to have an ether linkage such as a pyran moiety in the
chemical structure. Among the prenyl flavanones isolated from
Tephrosia apollinea L., the most active antifeedants proved to be
decided to expand our group of tested substrates by adding a
flavone derivative with an amino group at C-7 in ring A. The
antifeedant activity of synthetic aminoflavones toward plant
pests, especially aphids, has not been investigated, so far. We
expected that comparing the results of antifeedant activity of
chromones, chromanones, and the selected flavanones and
chalcones, which are precursors of flavonoids, would allow us to
determine which structural elements of the compounds are
necessary for subsequent reduced aphid settling.
The antifeedant activity of hop compounds, selected
synthetic chalcone derivatives, and chromones against the
peach-potato aphid (M. persicae [Sulz.]) was evaluated.
Synthetic pesticides, which are used against agricultural pests,
are highly toxic to humans and the environment. However,
these natural compounds were regarded as one of the plant’s
defensive systems against phytophagous insects along with the
peach potato plant surface. Our results showed that deterrent
properties changed depending on their structure, cyclic or not.
Isoxanthohumol (6), obtained by cyclization of xanthohumol
(14), had strong deterrent activity against the peach-potato
aphid, whereas its derivative, xanthohumol (14), was inactive.
As we have already mentioned, the presence of a 2′-OH group
63
compounds with a dihydrofuran ring. According to the
literature, good antifeeding activity was also observed for
64
compounds with a naphthalene substituent and chalcones
65,66
with electron acceptor groups in ring A.
The objective of our work was to obtain hop flavonoid
compounds and their derivatives of diverse relatively simple
chemical structures and to evaluate their antifeedant activity.
For the biological tests we have chosen two major prenylated
hop flavonoids, xanthohumol (14) and isoxanthohumol (6),
and an isoxanthohumol derivative without the prenyl and
methyl groups, naringenin (5), a flavonoid that is commonly
found in citrus fruits. As model compounds for this study,
flavone and flavanone derivatives were used without the phenyl
substituent, containing either a chromone or 4-chromanone
skeleton obtained by chemical synthesis and also flavones and
flavanones, which are structural analogues of natural phytoes-
trogens and their derivatives. To the group of compounds
67,68
described in the earlier works
and also for comparison, we
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in chalcones facilitates their cyclization to their isomeric forms,
flavones. The second major difference likely to affect the
activity is the existence in compound 14 of a strong
intramolecular hydrogen bond between the carbonyl group
the antifeedant activity. Our results indicate that the prenyl
group, and flavanones, rather than the flavonols and chalcones,
might make predominant contributions to antifeedant inhib-
ition. Therefore, prenylated flavonoids possessing lipophilic
moieties may be potent candidates for antifeedants. Our results
suggested that the antifeedant activity required not only the
important 2-position substituent but also the substituent
pattern on the A-ring and the hydrogenation of the C −C
1
and the hydroxyl group. On the H NMR spectrum it is
evidenced by the presence of a signal at δ 14.7 for the proton of
the 2′-OH group involved in a strong intramolecular hydrogen
1
8
bond. The carbonyl group of isoxanthohumol (6) for obvious
reasons is not involved in such binding. According to the
literature, the observed differences in activity may also arise
from inhibition of the activity of the enzymes involved in the
detoxification of xenobiotics, for example, cytochrome P450
2
3
double bond of these insect antifeedants, flavonoids and
67
chromones. Similar results were reported by Morimoto et al.
In our study the introduction of an additional amino group at
C-7 to flavone (9) caused an increase in antifeedant activity
against the peach-potato aphid. This is a first report about the
feeding deterrent activity of aminoflavones in the literature.
Significant correlations were found between biological activity
and molecular size of the derivatives with a chromone system.
The presence of a phenyl group at C-2 of chromone (7) and
the introduction of an amino group at C-7 in the flavone (8)
resulted in an increase in the deterrent activity, which was
observed during the longer time. The relationship between
physicochemical properties and insect antifeedant activity of
6
9
enzymes. The compounds selected for the study showed
various degrees of feeding detterent activity. In our study,
flavanones, chromanones, and chalcones having hydroxyl
groups did not show any insect antifeedant activity. The most
inactive was a 4-hydroxychalcone (11), which was an attractant.
An additional substituent of a hydroxyl group at the para
position in ring B of a chalcone decreased the antifeedant
activity, compared to the unsubstituted chalcone (10). The
structure−activity analysis led to the conclusion that acylation
of the hydroxyl group in ring B of chalcone 11 results in an
increase of the antifeedant activity, compared to the molecule
with the free OH group. The presence of hydroxyl groups in
the molecule of naringenin (5) had a considerable influence on
the antifeedant activity, compared to the unsubstituted
flavanone (4), which was only weakly active. As in the case
of other biological activity, moderate deterrent properties of
polyphenolic compounds, including naringenin (5), stem from
the presence of the reactive hydroxyl groups, which facilitate
binding to enzyme active sites as well as formation of hydrogen
bonding with enzyme system in aphids. These result in a
change of their metabolism. Flavonoids 4, 8, and 9, especially,
have no hydroxy substituent on the A-ring. Recent research
confirming the antifeedant activity of naringenin (5) and its
derivatives indicates that generalizations concerning the
structure−activity relationships of the mentioned compounds
74
compounds has been reported by Morimoto et al.
Among several pest control strategies (comprising mechan-
ical, agrotechnical, and chemical methods), biological methods
of crop protection that employ compounds of plant origin
(including flavonoids) are best accepted in organic food
production. Therefore, this biological method of plant
protection should be recommended, which is confirmed by
the results of laboratory tests.
In the next step of the research an optimization of the
chemical structure of these compounds is needed. This will
involve computational methods such as QSAR models that
relate experimentally measured biological activities of com-
67
pounds to their molecular structure. Natural plant com-
pounds, such as hop flavonoids, may be applied as models or
substrates for the synthesis of highly specific substances that
inhibit feeding of pests.
34,70,71
cannot be applied to a wide range of pests
because the
AUTHOR INFORMATION
Corresponding Author
*(M.S.) Phone: +48 71 320 5468. Fax: +48 71 320 7744. E-
mail: monika.stompor@gmail.com.
above-mentioned compounds stimulated feeding behavior of
the insects, whereas another was the best feeding deterrent. As
describe in the literature, cleavage of the ether linkage of the
■
67
pyran ring of flavanoids and the hydrogenation of the α,β-
unsaturated bond in chalcones decrease the antifeedant
Funding
7
2
activity. Ohmura et al. reported that a dihydrochalcone,
phloretin, has the same structure as naringenin, except for the
absence of the pyran ring, and showed less antifeedant activity
against the subterranean termite Coptotermes formosanus than
This work was financially supported by the National Science
Centre (Grant 2011/01/B/NZ9/02890), 2011−2014.
Notes
The authors declare no competing financial interest.
67
naringenin (5). As was reported by Morimoto et al., although
the decrease in the activity and the number of hydroxyl groups
were correlated, it was attributable to the penetrability toward
the receptor in the insect taste-sensitive organ. The substitution
of the flavonoid ring system with the prenyl unit and a −OCH3
group increases the lipophilicity and confers to the molecule a
strong affinity for biological membranes, which play an
important role in biomolecule transport, distribution, action,
and selectivity. The hop compounds intercalate into the lipid
bilayer, influencing its glycerol backbone region, hydrocarbon
chain region, and, to a lesser extent, polar headgroup region.
The calculation of log P values identified xanthohumol (4.38 ±
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