Bioorganic & Medicinal Chemistry Letters 24 (2014) 773–779

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Bioorganic & Medicinal Chemistry Letters

journal homepage: www.elsevier.com/locate/bmcl

Molecular interactions between terpenoid mosquito repellents

and human-secreted attractants
Shengliang Liao a, Jie Song b,⇑, Zongde Wang a,⇑, , Jinzhu Chen a, Guorong Fan a, Zhanqian Song c,
Shibin Shang c, Shangxing Chen a, Peng Wang a
a
College of Forestry, Jiangxi Agricultural University, Nanchang 330045, Jiangxi, China
b
Department of Chemistry and Biochemistry, University of Michigan-Flint, 303E Kearsley Street, Flint, MI 48502, USA
c
Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing 210042, Jiangsu, China

a r t i c l e i n f o a b s t r a c t

Article history: Molecular interactions between terpenoid mosquito repellents and three typical human-secreted attrac-
Received 19 November 2013 tants, ammonia, 1-octen-3-ol, and formic acid were studied. Relative energies, bond distances, and bond
Revised 20 December 2013 angles of the molecular interactions were obtained at HF level to evaluate the interaction intensity and
Accepted 24 December 2013
types. The effects of molecular interactions on repellency were investigated by the subsequent
Available online 2 January 2014
quantitative structure–activity relationship (QSAR) study. The results of this study suggest that attrac-
tant–repellent interaction should not be ignored and could be helpful for future research on the repelling
Keywords:
mechanism of mosquito repellents.
Terpenoid
Mosquito repellent
Ó 2014 Elsevier Ltd. All rights reserved.
Human-secreted attractant
Molecular interaction
Repellency

Mosquito repellents are a group of compounds which act to pre-
vent humans from mosquito biting.1 The spread of some fatal epi-
demic diseases,2 like malaria, which caused 1.17 million deaths in
2010, are caused by mosquito biting.3 Also, drug resistances be-
come more common. For example, Plasmodium falciparum (Welch)
has an increased resistance to anti-malarial drugs.4 These exem-
plify the reason why mosquitoes are causing more and more health
issues. Therefore, as a way to remedy this situation, repellent is
recommended as a way for personal protection, and thus, the
development of powerful mosquito repellents is extremely impor-
tant. Traditional mosquito repellent screening processes are
expensive and time-consuming. Quantitative structure–activity
relationship (QSAR) has therefore been applied to assist with this
process.5 However, only a few studies have investigated the quan-
titative relationships between chemical structures of mosquito
repellent and their repellency.6–11
Moreover, the repelling mechanism is still unclear and, to cer-
tain extents, controversial. The N,N-diethyl-3-methyl benzoyl
amide (DEET), which was discovered in 1954,12 has been one of
the most successful mosquito repellents used for decades.13
Numerous studies have been carried out in order to understand
⇑ Corresponding authors. Tel.: +1 8107623275; fax: +1 810 7666693 (J.S.);
tel.: +86 13870686011 (Z.W.).
E-mail addresses: jiesong@umich.edu (J. Song), zongdewang@163.com
(Z. Wang).
Co-corresponding author.
how this repellent works. Some researchers have confirmed that
DEET can block electrophysiological responses of olfactory sensory
neurons to attractive odors. Davis et al. found that DEET inhibits
lactic acid-sensitive neurons, a pair of chemoreceptor neurons in
the grooved-peg (A3) on the antennae of the mosquito, Aedes
aegypti.14 Recently, Ditzen et al. found that DEET strongly inhibited
1-octen-3-ol-evoked electrophysiological responses in Anopheles
gambiae and Drosophila melanogaster.15 Another opinion is that
the mosquito evades its host after its olfactory neuron is activated
by repellent DEET. Syed et al. identified an olfactory receptor neu-
ron (ORN) housed in a trichoid sensillum on the Culex quinquefas-
ciatus antennae that detects DEET in a dose-dependent manner.
This means that the mosquito endows with DEET-detecting ORNs,
to detect and avoid DEET.16 Dogan et al.17 found that DEET acts as
an attractant when a human host is absent and a repellent in the
presence of the host. Such observations are confusing and difficult
to explain. It may imply that attractants from human hosts may af-
fect some properties of ‘commercial repellents’ and the repelling
mechanism could be much more complicated than what one
would expect. The role of attractants from human hosts and their
potential effect on the repelling mechanism have been ignored in
most QSAR studies done so far.
It is known that, besides L-lactic acid, there are many attractant
compounds from skin emanation, for example, ammonia, 1-octen-
3-ol, and some short-chain carboxylic acids. Ammonia, ranging
from 17 lg/L to 17 mg/L, makes a significant contribution to the

0960-894X/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bmcl.2013.12.102
774 S. Liao et al. / Bioorg. Med. Chem. Lett. 24 (2014) 773–779

effect that may also contribute to repellency.16 Unfortunately,

H H OH O
N
H H OH
NH3 (3R)-1-Octen-3-ol Formic acid α-pinene
Scheme 1. Structures of three attractants, a-pinene and b-pinene.
mosquito (Aedes aegypti) attraction behavior when placed together
with lactic acid.18 1-octen-3-ol is believed to increase the attrac-
tiveness of L-lactic and CO2 in field studies.19 Bosch et al. found that
C1–C3 and C5–C8 carboxylic acids, over a wide range of concentra-
tion, could enhance the attractiveness of lactic acid.20 Furthermore,
Cork et al. also observed that formic acids elicit the largest ampli-
tude EAG response in the electroantennography (EAG) assay on
Anopheles gumbiae Giles.21 It is obvious that ammonia, 1-octen-
3-ol, some short-chain carboxylic acids, and etc make humans
attractive to mosquitoes. Recently, it was hypothesized that DEET
may suppress the release of physiologically relevant compounds,
such as the above attractants, after smeared on human skin. Mean-
ing, DEET altered the chemical profile of emanations by a ‘fixative’
more detail about the ‘fixative’ effect still remains mysterious. Be-
cause of the complicated roles of repellents and attractants, some
preliminary studies have started to focus on what happens be-
tween the repellents and attractants and how they may affect
β-pinene the repellency.22–26
In this study, ammonia, 1-octen-3-ol, and formic acid were
chosen as characteristic compounds from humans. To further
understand these compounds, molecular interactions were investi-
gated. Also, a group of terpenoid repellents as well as their effect
on the mosquito repellency were studied. Theoretical calculations
were performed to show how ammonia, 1-octen-3-ol, formic acid,
and repellents interact between each other. Subsequent QSAR
studies were used to elucidate how the complexes have an effect
on the repellency.
22 Six-member-ring terpenoid mosquito repellent compounds
were synthesized from a-pinene or b-pinene (Scheme 1). Their
repellency against Aedes albopictus was tested. Structural informa-
tion and repellency values of compounds were obtained from
former studies10,27, shown in Table 1.
Structures of three attractant molecules, twenty-two terpenoid
mosquito repellents, and the attractant–repellent complexes were
built and optimized using GaussView 4 and GAUSSIAN 03W software

Table 1
The interaction energy (in kJ/mol) calculated at HF level

No. Formula of structure Log CRR NH3-repellent 1-Octen-3-ol-repellent Formic acid-repellent

O
O CH3
1 1.767155866 8.3 15.8 20.7

O
O C2H5
2 1.803457116 15.3 16.7 21.0

OH
3 1.861534411 13.0 8.6 25.5
OH

O H
4 1.954242509 10.3 10.2 23.1

OH

O
O CH3
5 1.908485019 19.9 10.5 21.0

OH
O
O C2H5
6 1.857332 19.9 14.0 26.1

OH

7 1.72427587 14.1 10.6 19.6

OH

O
8 1.587710965 13.8 16.8 21.7
O

O
9 1.607455023 14.7 16.5 19.0
O C2H5

OH
10 1.838849091 12.6 10.5 22.2
 S. Liao et al. / Bioorg. Med. Chem. Lett. 24 (2014) 773–779 775

Table 1 (continued)

No. Formula of structure Log CRR NH3-repellent 1-Octen-3-ol-repellent Formic acid-repellent

OMe
11 1.716837723 12.1 13.4 16.4

OC2H5
12 1.793790385 13.7 12.8 17.2

O
13 1.860338007 13.5 11.8 17.7

O
14 O H 1.748962861 10.2 14.2 24.1

OCOCH3
15 1.783903579 14.3 16.0 21.5

OCOC2H5
16 1.808885867 15.0 14.6 18.2

O
17 1.5774918 12.7 8.3 15.5

18 1.72427587 14.3 18.5 19.4

CH2CH2OCOCH3

19 1.754348336 14.4 17.1 19.3

CH2CH2OCOC2H5

20 OCOCH3 1.700703717 12.9 17.3 18.5

21 OCOCH3 1.713490543 15.9 16.0 18.5

22 1.711807229 13.7 14.0 18.2

OCOCH3
Mean 13.8 13.8 20.2

package, respectively.28 Geometry optimizations of these confor-
mations were done at the HF/6-31G(d) level. Interactions were
considered between hydroxyl, carbonyl, and etheric groups in
repellents and hydroxyl, carbonyl, and amine groups in other char-
acteristic compounds. Characteristic compounds were allowed to
rotate along repellents to have all possible conformations. After
geometry optimizations, the most stable conformations were se-
lected and geometrical parameters were obtained. Interaction
energies between attractants and repellents are calculated by:
EðinteractionÞ ¼ EðARÞ  EðAÞ  EðRÞ
E(interaction) represents the interaction energy, E(A) represents en-
ergy of the attractant, E(R) represents energy of the repellent com-
pound and E(AR) represents energy of the complex.
Figure 1 shows the structures of three complexes formed be-
tween three attractants and repellent (compound 1). Besides repel-
lents and complexes (formed by repellents and characteristic
compounds), specific fragments were defined to describe the area
contributing to molecular interactions (see Fig. 1, the fraction of
the molecule in red boxes were defined as fragments). Six types
of descriptors, namely, constitutional descriptor, topological
descriptors, geometrical descriptors, electrostatic descriptors,
quantum-chemical descriptors, and thermodynamic molecular
descriptors were calculated. More than 800 descriptors of repel-
lents, fragments, and complexes (formed by repellents and charac-
teristic compounds) were calculated by Ampac 8.16 and Codessa
2.7.10 software.
Heuristic method, encoded in Codessa 2.7.10 software, was em-
ployed to screen significant descriptors to build multilinear QSAR
models. To avoid the ‘over-parameterization’ of the models, an
increasing R2 value less than 0.02 was chosen as the breaking-point
criterion.29 The robustness and predictive ability were validated by
‘leave-one out’ cross validation and internal validation, which are
referred.7,29,30 The 22 compounds were divided into three groups
for internal validation. Group A includes compounds 1, 4, 7, 10,
13, 16, 19, 22, group B includes 2, 5, 8, 11, 14, 17, 20, and group
C includes 3, 6, 9, 12, 15, 18, 21. Internal three fold cross-validation
was performed.
The interaction energies as well as hydrogen bonds are listed in
Tables 1–4 respectively. From the structures of three attractants, it
is clear that formic acid could supply the carboxyl group to form
the hydrogen bonding and ammonia and 1-octen-3-ol could do-
nate the nitrogen and alcohol hydroxyl group. Because of the pres-
ence of the adjacent carbonyl moiety, the O–H group is more
polarized than the O–H group of alcohols or the N–H group; thus,
it enhances the dipole strength. As a result, the dipoles in carbolic
acids allow these compounds to participate in energetically favor-
able hydrogen bonding (H-bonding) interactions with repellents,
functioning as both an H-bond donor and acceptor. From Table 1,
it confirms that the interaction energies between formic acid and
repellents (about -20 kJ/mol) are generally stronger than those be-
tween ammonia and 1-octen-3-ol and repellents (about -14 kJ/
mol). It can be seen, from Table 4, that formic acids could form
the shortest bond length and optimal bond angles.
776 S. Liao et al. / Bioorg. Med. Chem. Lett. 24 (2014) 773–779

QSAR models are obtained by linear regression method, using

Figure 1. Complexes formed between three attractants and repellent.
the descriptors screened out by heuristic method, while the cross
validation coefficient and F value are employed to be the selection
standard of model. Due to the collinearity control carried out
during the heuristic screening, any two descriptors are found
non-collinear (R2nc 60.5345, default value R2nc = 0.65).31 Table 5
shows descriptors obtained in the best QSAR models.
Both ‘leave-one out’ cross-validation (LOOCV) and threefold
cross-validation are performed to validate the optimal models.
The results are listed in Table 6. Validations are carried out by
dividing the parent data into three subsets A, B, and C, with 8, 7,
and 7 compounds, respectively. Training sets are a combination
of two subsets with the third one as the test set. The correlation
equation using the same descriptors was derived from training sets
and used to predict values for the corresponding test sets. Due to
the smaller size of test sets, it is not surprising to observe the dis-
persive predicted R2. For cases of ammonia and 1-octen-3-ol, the
average R2 (pred) of all test sets still gives satisfactory results com-
pared to the average R2 (fit) of all training sets. For the case of for-
mic acid, relatively large deviation of R2 (fit) from R2 (pred) is
observed and it is believed due to three descriptors instead of four
descriptors in the other two cases. Figure 2 gives the comparison
between experimental values (log CRR) and predicted values
(log CRR) from QSAR models listed in Table 5. All three cases dem-
onstrate excellent linear relationship (R2 >0.93 for all three cases).
Therefore, it is reasonable to believe that QSAR models obtained
are statistically significant.
Descriptors involved in the qualitative model obtained could
supply some information to help us understand possible factors
that may affect the repelling mechanisms. In the case of ammo-
nia, the first statistically important descriptor is MO-related,32
which is related to HOMO energy, an indicator of the electropho-
bic effect.33 It is likely a factor that will affect the electronic prop-
erty of the repellent and, therefore, alter the contribution to
intermolecular forces. When ammonia is present, it may indicate
the popularity to accept the lone pair on N. The second one is the
electron–electron repulsion energy, a quantum-chemical descrip-
tor. The third one is another MO-related descriptor, which is
related to HOMO–LUMO energy gap and the stability of the repel-
lent molecule. The last one is ZX Shadow/ZX Rectangle, a geomet-
rical descriptor reflecting the size and geometrical shape of the

Table 2
Interaction distances and angles of ammonia-repellent complexes

No. Interaction type Distance (Å) Angle (°) No. Iinteraction type Distance (Å) Angle (°)
1 >NH  O@C< 2.301 169.7 12 >NH  O< 2.510 100.3
>NH  O< 2.514 100.1
2 >NH  O@C< 2.496 102.1 13 >NH  O< 2.596 94.5
>NH  O@C< 2.418 107.2 >NH  O< 2.512 99.6
3 >NH  O< 2.411 106.9 14 >NH  O@C< 2.274 154.3
>NH  O< 2.435 105.3
4 >N-  HO- 2.692 169.5 15 >NH  O@C< 2.527 98.6
>NH  O@C< 2.511 99.5
5 >NH  O< 2.265 138.6 16 >NH  O@C< 2.329 113.8
>NH  O@C< 2.369 115.7
6 >NH  O< 2.253 140.0 17 >NH  O< 2.504 103.3
>NH  O@C< 2.369 115.8 >NH  O< 2.396 110.6
7 >NH  O< 2.363 110.1 18 >NH  O@C< 2.339 112.4
>NH  O< 2.585 95.9
8 –NH  O@C< 2.161 179.7 19 >NH  O@C< 2.348 111.9
9 >NH  O@C< 2.525 98.6 20 >NH  O@C< 2.163 176.5
>NH  O@C< 2.541 97.6
10 >NH  O< 2.426 106.8 21 >NH  O@C< 2.472 103.6
>NH  O< 2.430 106.5 >NH  O@C< 2.426 106.6
>NH  O< 3.942 118.9
11 >NH  O< 2.578 95.2 22 >NH  O@C< 2.637 92.5
>NH  O< 2.530 98.0 >NH  O@C< 2.406 106.8
 S. Liao et al. / Bioorg. Med. Chem. Lett. 24 (2014) 773–779 777

Table 3
Interaction distances and angles of 1-octen-3-ol-repellent complexes

No. Interaction type Distance (Å) Angle (°) No. Interaction type Distance (Å) Angle (°)
1 –OH  O@C< 2.155 144.5 12 –OH  O< 2.155 151.8
2 –OH  O@C< 2.181 148.3 13 –OH  O< 2.187 155.6
3 –OH  O< 2.179 164.2 14 –OH  O@C< 2.196 169.6
–OH  O< 2.531 121.7
4 –OH  O@C< 2.227 160.7 15 –OH  O@C< 2.165 137.1
–OH  O< 2.363 141.4
5 –OH  O@C< 2.214 155.8 16 –OH  O@C< 2.627 152.1
–OH  O< 2.176 132.1
6 –OH  O@C< 2.173 166.7 17 –OH  O< 2.184 162.7
7 –OH  O< 2.172 163.6 18 –OH  O@C< 2.191 153.8
8 –OH  O@C< 2.185 177.6 19 –OH  O@C< 2.183 163.8
–OH  O< 2.466 125.8
9 –OH  O@C< 2.186 174.8 20 –OH  O@C< 2.186 173.7
–OH  O< 2.385 127.6
10 –OH  O< 2.148 161.9 21 –OH  O@C< 2.159 139.4
11 –OH  O< 2.187 154.5 22 –OH  O@C< 2.221 138.5

Table 4
Interaction distances and angles of formic acid–repellent complexes

No. Interaction type Distance (Å) Angle (°) No. Interaction type Distance (Å) Angle (°)
1 –OH  O@C< 2.131 172.3 12 –OH  O< 2.081 174.3
2 –OH  O@C< 2.131 172.4 13 –OH  O< 2.090 159.3
3 –OH  O< 2.081 146.7 14 –OH  O@C< 2.088 166.8
4 –OH  O@C< 2.172 172.8 15 –OH  O@C< 2.102 179.7
>C@O  HO– 2.354 167.9
5 –OH  O@C< 2.150 175.0 16 –OH  O@C< 2.136 177.2
6 –OH  O@C< 2.206 146.4 17 –OH  O< 2.151 170.3
>C@O  HO– 2.436 161.7
7 –OH  O< 2.096 163.6 18 –OH  O@C< 2.130 177.2
8 –OH  O@C< 2.100 178.8 19 –OH  O@C< 2.131 177.8
9 –OH  O@C< 2.111 172.9 20 –OH  O@C< 2.124 177.0
10 –OH  O< 2.106 150.5 21 –OH  O@C< 2.123 175.6
>C@O  HO– 2.140 121.0
11 –OH  O< 2.133 179.0 22 –OH  O@C< 2.138 168.2

Table 5
QSAR models

No. Coefficient Coefficient error t-Test Descriptors

Ammonia-repellent model
R2 = 0.9471, R2cv = 0.9173, RMSE = 0.0219, s2 = 0.0005, F = 76.13, n = 22, log CRR1 = 2.35  222.48A1  0.32A2 + 1.40A3 + 0.28A4
A0 2.35 0.08 28.28 Intercept
A1 222.48 22.26 9.99 Ma—Min nucleoph. react. index for an C atom
A2 0.32 0.03 9.68 M—Min e–e repulsion for an H atom
A3 1.40 0.36 3.91 M—Max 1-electron react. index for an C atom
A4 0.28 0.08 3.56 fb—TerNH3–ZX Shadow/ZX Rectangle
1-Octen-3-ol-repellent model
R2 = 0.9369, R2cv = 0.8998, RMSE = 0.0240, s2 = 0.0007, F = 63.04, n = 22, log CRR2 = 42.49 + 2.35B1  224.80B2 + 1.83B3  0.60B4
B0 42.49 15.00 2.83 Intercept
B1 2.35 0.30 7.85 M—FHBCA Fractional HBCA (HBCA/TMSA)
B2 224.80 23.47 9.58 M—Min nucleoph. react. index for an C atom
B3 1.83 0.37 4.91 COMc—Max 1-electron react. index for an C atom
B4 0.60 0.22 2.72 f—TerOCT-exch. eng. + e–e rep. for an H–O bond
Formic acid-repellent model
R2 = 0.9374, R2cv = 0.9040, RMSE = 0.0239, s2 = 0.0007, F = 89.89, n = 22, log CRR3 = 2.89  212.45C1  0.31C2 + 0.85C3
C0 2.89 0.09 30.57 Intercept
C1 212.45 19.19 11.07 M—Min nucleoph. react. index for an C atom
C2 0.31 0.03 10.08 M—Min e–e repulsion for an H atom
C3 0.85 0.18 4.76 COM—ESP-Min net atomic charge for an O atom
a
M—is a prefix which means descriptor calculated from repellent itself.
b
f—is a prefix which means descriptor calculated from fragment in the complex.
c
COM—is a prefix which means descriptor calculated from attractant–repellent complex.
778 S. Liao et al. / Bioorg. Med. Chem. Lett. 24 (2014) 773–779

Table 6 2.00
Validation of QSAR models
1.95
Model R2 R2cv Training R2fit Test set R2pred y= -9.0909E-6+x
1.90

Experimental value (logCRR)

set (training set) (test set) R2=0.9471
Ammonia- 0.9471 0.9173 AB 0.9516 C 0.9166 1.85
repellent AC 0.8641 B 0.9529
1.80
BC 0.9697 A 0.9088
Mean 0.9285 0.9261 1.75
1-Octen-3-ol- 0.9369 0.8998 AB 0.9115 C 0.9066 1.70
repellent AC 0.8898 B 0.9188
BC 0.9645 A 0.8969 1.65
Mean 0.9219 0.9047 1.60
Formic acid- 0.9374 0.9040 AB 0.9614 C 0.8158
1.55
repellent AC 0.9243 B 0.9371
BC 0.9562 A 0.8889 1.55 1.60 1.65 1.70 1.75 1.80 1.85 1.90 1.95 2.00
Mean 0.9473 0.8806
Calculated value (logCRR)
(a) Ammonia-repellent model

2.00
fragment on the complex between the repellent and ammonia. It 1.95
is similar to the previous study,24 where the electrostatic interac- y= -4.5455E-6+x
1.90

Experimental value (logCRR)

tion caused by the electron distribution and the specific orienta- 2
R =0.9369
tion/geometry of the repellent-attractant complex are statistically 1.85
important. For 1-octen-3-ol, the first descriptor is fractional 1.80
H-bonding charged surface area, defined by the ratio of H-bond-
1.75
ing charged surface area over total molecular surface area. It is a
charged-partial surface area (CPSA) descriptor, related to the elec- 1.70
tron distribution on the surface as well as intermolecular interac- 1.65
tions. The second one, same as the first one in the case of 1.60
ammonia, is an indicator of the electron-acceptance. The third
1.55
one, MO-related one-electron reaction index, is an indicator of
the HOMO–LUMO energy gap, which is related to the stability 1.55 1.60 1.65 1.70 1.75 1.80 1.85 1.90 1.95 2.00
of repellent–attractant complex. The last one is a quantum-chem- Calculated value (logCRR)
ical descriptor, related to electronic exchange energy and elec- (b) 1-octen-3-ol-repellent model
tronic repulsion inside the fragment. All these descriptors imply
that the possible interaction between the repellent and 1-octen- 2.00
3-ol as well as the strength of such interactions could be very
1.95
important. y= -9.0909E-6+x
Experimental value (logCRR)

Unlike ammonia and 1-octen-3-ol, only three descriptors are 1.90 2

R =0.9374
kept in the final QSAR equation for formic acid. The first two are 1.85
same as the case of ammonia. The third one is an electrostatic 1.80
descriptor, reflecting the charge distribution on oxygen atoms in
1.75
the repellent-attractant complex and then electrostatic interac-
tions between the repellent and formic acid. 1.70
Though different descriptors are obtained in each case, most of 1.65
them are related. All three cases show that the electron distribu-
1.60
tion on the repellent is important and as a result, affects the possi-
ble interactions between the repellent and attractant. In addition, 1.55
statistically important descriptors related to the fragment/complex 1.55 1.60 1.65 1.70 1.75 1.80 1.85 1.90 1.95 2.00
between repellent and attractant are found in each case. It implies Calculated value (logCRR)
that the interactions between the repellent and the attractant may
(c)Formic acid-repellent model
be a factor that cannot be ignored in studying the repelling mech-
anism. Both those observations are similar to our previous studies Figure 2. Comparison of the experimental value (log CRR) and predicted value
on repellents and lactic acids.24 (log CRR) for three models.
Molecular interactions have been theoretically investigated be-
tween three attractants (ammonia, 1-octen-3-ol, and formic acid)
and twenty-two terpenoid mosquito repellent compounds. The Acknowledgments
calculated interaction energies and molecular distances confirm
relatively stronger molecular interactions between the attractant This work has been supported by the Special Fund of National
molecule and the repellent molecule. QSAR study further shows Forestry Public Welfare Scientific Research Project of China
that some descriptors related to the repellent–attractant com- (201304602), the Major Disciplines Academic and Technical Leader
plexes are statistically important. This is different from previous Training Program of Jiangxi Province (20133BCB22004), Science
studies where descriptors from only the repellent were considered. and Technology Support Program of Jiangxi Province
It may imply that systematic study should be conducted experi- (20132BBF60057), the International S&T Cooperation Program of
mentally and theoretically to find the relationship among the host, China (2011DFA32440), and RCAC Award from the University of
repellent, and attractant. Michigan-Flint.
 S. Liao et al. / Bioorg. Med. Chem. Lett. 24 (2014) 773–779 779

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