Design, synthesis and insecticidal activity of novel semicarbazones and thiosemicarbazones derived from chalcone

Article abstract of DOI:10.1080/14786419.2020.1739679

Thirty semicarbazone and thiosemicarbazone derivatives (2a–w and 4a–g) from chalcones containing furan and thiophene ring were designed and synthesized. They were characterized by IR, ¹H NMR, ¹³C NMR and HRMS. The crystal structure o

Full text of DOI:10.1080/14786419.2020.1739679

Natural Product Research
Formerly Natural Product Letters
ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: https://www.tandfonline.com/loi/gnpl20
Design, synthesis and insecticidal activity of novel
semicarbazones and thiosemicarbazones derived
from chalcone
Wei Cheng, Tingting Xiao, Weifeng Qian, Tong Lu, Tingting Zhang & Xiaorong
Tang
To cite this article: Wei Cheng, Tingting Xiao, Weifeng Qian, Tong Lu, Tingting Zhang &
Xiaorong Tang (2020): Design, synthesis and insecticidal activity of novel semicarbazones
and thiosemicarbazones derived from chalcone, Natural Product Research, DOI:
10.1080/14786419.2020.1739679
To link to this article: https://doi.org/10.1080/14786419.2020.1739679
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NATURAL PRODUCT RESEARCH
https://doi.org/10.1080/14786419.2020.1739679
Design, synthesis and insecticidal activity of novel
semicarbazones and thiosemicarbazones derived
from chalcone
Wei Cheng, Tingting Xiao, Weifeng Qian, Tong Lu, Tingting Zhang and
Xiaorong Tang
School of Science, Xihua University, Chengdu, China
ABSTRACT
ARTICLE HISTORY
Received 15 October 2019
Accepted 3 March 2020
Thirty semicarbazone and thiosemicarbazone derivatives (2a–w
and 4a–g) from chalcones containing furan and thiophene ring
were designed and synthesized. They were characterized by IR, H
1
NMR, 13C NMR and HRMS. The crystal structure of compound 2r
was characterized by single crystal X-ray diffraction. It crystallizes
in the monoclinic system with space group P21/c. The insecticidal
activity of the synthesized compounds was screened against
Leucania separata and Pieris rapae using beta-cypermethrin as the
comparative standard. The results displayed that most of them
had remarkable insecticidal activity. Among them, compounds
2e–g showed better activity than beta-cypermethrin against L.
separata and P. rapae. Compound 2p also possessed a better
activity than beta-cypermethrin against P. rapae. The insecticidal
activities of these compounds have been reported for the first
time.
KEYWORDS
Insecticidal activity;
Leucania separata; Pieris
rapae; semicarbazone;
thiosemicarbazone
CONTACT Xiaorong Tang
tangxiaorong0901@126.com
Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2020.1739679.
ß 2020 Informa UK Limited, trading as Taylor & Francis Group

2
W. CHENG ET AL.
1. Introduction
Leucania separata is a crop pest with serious harm. It usually eats seedlings of plants,
especially, maize, causing them to wither or disappear. Similarly, Pieris rapae is also a
vegetable pest which can cause serious harm. It often devours leaves of plants includ-
ing cabbage, which hinders their growth and even makes them die. In the past few
decades, insecticides including dimethoate, omethoate and methomyl have been used
to control these pests. However, their development of resistance to these insecticides
has reduced the efficacy of insecticidal treatments (Yang et al. 1995; Peng et al. 1996).
Therefore, the research and development of new pesticides against these pests are
continually necessary (Cao et al. 2002; Xu et al. 2003; Zheng et al. 2003; Di et al. 2007;
Liu et al. 2008).
Chalcones (1,3-diphenyl-2-propen-1-one) are an important class of natural prod-
ucts existing in various plants. They can also be obtained by chemical syntheses.
They have been widely used as synthons in the synthetic field because they have
the conjugated C ¼ C and C ¼ O double bonds, which can undertake various chem-
ical reactions. Furthermore, chalcone derivatives have diverse and interesting bio-
logical properties including insecticidal activity (Figure S1) (Gao et al. 2001; Hou
et al. 2002; Chen et al. 2007; Tao et al. 2007). Therefore, the discovery of novel chal-
cone derivatives with insecticidal activities attracts a great deal of attention around
the world.
Semicarbazones and thiosemicarbazones are also important compounds. They con-
tain the following scaffolds: NH2–CO–NH–N ¼ C< and NH2–CS–NH–N ¼ C<, respect-
ively. Researches and development of their analogues play an important part in the
pharmaceutical and insecticidal fields (Salgado and Hayashi 2007; Xue et al. 2007; Gan
et al. 2014; Liu et al. 2014). Moreover, their derivatives usually exhibit good selectivity
and low toxicity to non-target organisms (Alam et al. 2010; Aly et al. 2010). Therefore,
compounds containing semicarbazones or thiosemicarbazones have huge potential in
the agricultural field. It is necessary to discover their derivatives that have excellent
insecticidal activity and novel structures.
In the current study, 30 semicarbazone and thiosemicarbazone derivatives were
designed and synthesized by introducing semicarbazone or thiosemicarbazone moiety
into chalcones (Figure S2). Meanwhile, their insecticidal activities against L. separata
and P. rapae were evaluated in the laboratory to discover novel insecticides or lead
compounds with simple structures and excellent performances. To the best of our
knowledge, although the antifungal activities of them were reported in the two
Chinese invention patents published by our research group (Tang, Yang, Gao, Liu,
Gao, Xu et al. 2016; Tang, Yang, Gao, Liu, Gao, Zhang et al. 2016), their insecticidal
activities have been discovered for the first time.
2. Results and discussion
2.1. Chemistry
The syntheses and chemical structures of the target compounds are shown in
Scheme 1. The syntheses of the designed compounds were performed according to

NATURAL PRODUCT RESEARCH
3
R2
X
O
C
O
CHO
X
R2
R1
R1
1
a
Y
CHO
O
NH2
b
c
H2N
N
H
R2
5''
O
X
Y
2
O
3
4''
N
1
R1
N
H
2''
H2N
3''
1'
3
2'
6'
5'
R1
O
NH2
3'
4'
d
N
H
H2N
2a-w
5''
O
O
2
4
4''
1
N
2''
H2N
N
3''
3
5
H
1'
2'
6'
R1
5'
3'
4'
4a-g
: X = O, Y = O, R1 = 4-F, R2 = H
2a
: X = O, Y = O, R1 = 4-Cl, R2 = H
: X = O, Y = O, R1 = 4-Br, R2 = H
2b
2c
: X = O, Y = S, R1 = 4-Cl, R2 = H
2f
: X = O, Y = O, R1 = 3-Br, R2 = H
: X = O, Y = S, R1 = 4-F, R2 = H
2d
2g
2e
: X = O, Y = S, R1 = 4-Br, R2 = H
: X = O, Y = S, R1 = 4-Ph, R2 = H
: X = S, Y = O, R1 = 4-F, R2 = H
2i
2h
: X = S, Y = O, R1 = 4-Cl, R2 = H
: X = S, Y = O, R1 = 4-Br, R2 = H
: X = S, Y = O, R1 = 4-Ph, R2 = H
2j
2k
2l
: X = S, Y = O, R1 = 3-Cl, R2 = H
: X = S, Y = O, R1 = 3-Br, R2 = H
2n
: X = S, Y = O, R1 = 3,4-Cl
2 = H
2, R
2m
2o
: X = S, Y = S, R1 = 4-F, R2 = H
: X = S, Y = S, R1 = 4-Cl, R2 = H
2q
: X = S, Y = S, R1 = 4-Br, R2 = H
: X = S, Y = S, R1 = 4-F, R2 = Br
2p
2r
: X = S, Y = S, R1 = 4-Ph, R2 = H
: X = S, Y = S, R1 = 3-Cl, R2 = H
2s
2t
2u
: X = S, Y = S, R1 = 4-Cl, R2 = Br
: X = S, Y = S, R1 = 4-Br, R2 = Br
2w
: R1 = 4-F
: R1 = 4-Cl
4b
2v
4a
= 3-Br
= 2,4-Cl
= 3,4-Cl
: R1 = 4-Br
: R1 = 4-Ph
: R1
: R1
4f
: R1
4g
4c
4d
4e
2
2
Scheme 1. Synthetic method of target compounds 2a–w and 4a–g. Reagents and conditions: (a)
EtOH/NaOH, 0–5ꢀC; (b) EtOH/HOAc, 70ꢀC, 20 h; (c) EtOH/NaOH, 0–5ꢀC; (d) EtOH/HOAc, 70ꢀC, 20 h
the methods reported previously and modified appropriately (Qian et al. 2010; Zhang
1
et al. 2011). The structures of compounds 2a–w and 4a–g were confirmed by IR, H
NMR, 13C NMR and HRMS. The results showed that their spectrum data were in
agreement with the proposed structures.

4
W. CHENG ET AL.
Using compound 2r as an example, the elucidations of its structure are described
as follows:
IR(KBr) vmax (cm–1): 3403, 3267, 3157 (NH2, NH); 1599, 1477, 848 (Phenyl); 1384 (C-
1
N); 950 (H-C ¼ C-H, E-configuration); H NMR (300 MHz, DMSO-d6) d (ppm): 9.03 (s, 1H,
0
0
NH), 8.50 (s, 1H, NH2), 8.17 (s, 1H, NH2), 7.80 (d, J ¼ 7.8 Hz, 2H, C2 -H, C6 -H), 7.55 (d,
00
0
0
00
J ¼ 4.8 Hz, 1H, C3 -H), 7.28 (d, J ¼ 7.8 Hz, 2H, C3 -H, C5 -H), 7.19 (s, 1H, C5 -H), 7.05–7.03
(m, 1H, C4 -H), 6.87 (d, J ¼ 16.2 Hz, 1H, C2-H), 6.58 (d, J ¼ 15.9 Hz, 1H, C3-H); 13C NMR
00
(75 MHz, DMSO-d6) d (ppm): 178.40 (C ¼ S), 149.21 (C-1), 141.45 (C-200), 133.01 (C-30, C-
50), 131.04 (C-20, C-60), 130.01 (C-10), 129.88 (C-500), 129.52 (C-300), 128.72 (C-400), 127.75
(C-3), 127.57 (C-40), 123.79 (C-2).
2.2. Crystal structure analysis of compound 2r
The molecular structure of compound 2r was determined by single crystal X-ray dif-
fraction and is shown in Figure S3. Its crystal data and structure refinement are pre-
sented in Table S1. Its crystallographic information file is deposited at the Cambridge
Crystallographic Data Center (CCDC No. 1405000). The selected structure parameters
are displayed in Table S2.
As shown in Table S2 and Figure S3, the thiophene ring, C11–C14, N1–N3 and S2
are located in a plane. The dihedral angle between the plane and the phenyl ring is
67.1(6)ꢀ. The double bond between C11 and C12 forms an E-configuration, whereas
the double bond between C13 and N1 presents a Z-configuration. The compound
exhibits two intermolecular hydrogen bonds N3–H3Aꢁ ꢁ ꢁBr1 and N3–H3Bꢁ ꢁ ꢁS2. Their
bond length is 2.849 Å and 2.707 Å, respectively. Their bond angle is 153.04ꢀ and
156.28ꢀ, respectively.
2.3. Insecticidal activity
Compared with the efficient insecticide beta-cypermethrin, all the synthesized com-
pounds were submitted to laboratorial bioassay using L. separata and P. rapae as tar-
gets. The results are displayed in Tables S3 and S4. Compounds 2e–g and 2p
displayed the best insecticidal activity. The insecticidal activity of 2e–g against L. sepa-
rata was even superior to beta-cypermethrin. The activity of 2e–g and 2p also sur-
passed beta-cypermethrin against P. rapae. 2p–r and 4e exhibited excellent activity
against L. separata and their LC50 values were close to beta-cypermethrin. Likewise,
the activity of 2q, 2r and 4b was also close to beta-cypermethrin against P. rapae. 2d
and 2h displayed good activity against L. separata and their LC50 values were 2.72 and
2.98 lg mLꢂ1, respectively. Similarly, 2n, 2s, 4d and 4e showed good insecticidal activ-
ity against P. rapae.
According to the results of 2a–c, 2e–g, 2i–m and 2p–t, it could be found that the
activity of thiosemicarbazone derivatives was better than that of semicarbazone deriv-
atives. If the activity of 2p–r was compared with that of 2u–w, respectively, it was
obvious that when the hydrogen atom at position-5 of the thiophene ring was substi-
tuted by a bromine atom, the insecticidal activity of corresponding compound
decreased. When the results of 2c, 2k and 4c were compared with those of 2d, 2n

NATURAL PRODUCT RESEARCH
5
and 4e, respectively, it could be known that the compounds with a bromine atom at
position-3 of the phenyl ring displayed a better activity than those with a bromine
atom at position-4 of the phenyl ring, the cause of which needs to be further found
out. However, in accordance with the results of 2j, 2m, 2q and 2t, it could be found
that the compounds with a chlorine atom at position-4 of the phenyl ring exhibited a
better activity than those with a chlorine atom at position-3 of the phenyl ring, which
also needs to be further studied.
Although a definite structure-activity relationship could not be found through the
above-mentioned findings, the interesting results obtained can be used for designing
and synthesizing more analogues to further study their quantitative structure-activity
relationship so that more bioactive compounds or lead compounds may
be discovered.
3. Experimental
3.1. General
3.1.1. Biomaterials
Leucania separata was reared for generations in the laboratory. It was maintained at
22–24 ꢀC, 60% relative humidity (RH) and 14:10 h light: dark photoperiod. Third-instar
larvae of L. separata were used in the experiments. P. rapae was reared for generations
in the laboratory. It was held at 24–26 ꢀC, 75–95% RH and 12:12 h light: dark photo-
period. Third-instar larvae of P. rapae were used in the experiments.
3.1.2. Instrument and reagent
All chemicals and solvents were purchased from commercial sources unless specified
otherwise. IR spectra were recorded on a Nicolet 380 spectrometer. NMR spectra (1H
NMR and 13C NMR) were taken on a Bruker 300 MHz spectrometer using deuterated
dimethyl sulfoxide (DMSO-d6) as the solvent. HRMS data were taken on a LTQ Orbitrap
Elite mass spectrometer. Melting points were determined using an X-4B micro-melting
point apparatus and were not corrected.
3.2. Preparation of intermediates 1 and 3
As shown in Scheme 1, the derivative of acetophenone (0.01 mol) was dissolved in
anhydrous ethanol (10 mL). 10% NaOH solution (5 mL) was added to the solution. The
mixture of selected aldehyde (0.01 mol) and anhydrous ethanol (10 mL) was slowly
added to the above solution in an ice box under stirring. The reaction was kept at
0–5 ꢀC and monitored by thin layer chromatography (TLC) at 254 nm, whose developer
was the mixture of petroleum ether (60–90 ꢀC) and ethyl acetate in the ratio of 3:1(by
volume). After the reaction was completed, distilled water was added to the reaction
mixture. The pH value of the solution was adjusted to about 7 by 10% HCl. The solid
that precipitated was filtered and washed with distilled water. The crude products
were recrystallized from anhydrous ethanol to give intermediates 1 and 3.

6
W. CHENG ET AL.
3.3. Synthetic procedure for target compounds
According to Scheme 1, semicarbazide or thiosemicarbazide (0.015 mol) was dissolved
in 95% ethanol (20 mL). Glacial acetic acid (1.5 mL) was added to the solution.
Intermediate 1 or 3 (0.015 mol) was completely dissolved in anhydrous ethanol
(30 mL). Under stirring, the solution containing the intermediate was slowly added to
the above mixture. The reaction continued about 20 h at 70 ꢀC. Its process was moni-
tored by TLC at 254 nm, whose developer was the mixture of petroleum ether
(60–90 ꢀC) and ethyl acetate in the ratio of 2:1(by volume). After the reaction was com-
pleted, the pH value of the solution was adjusted to about 7 by 10% NaOH. The solid
that precipitated was filtered and washed with distilled water. For 2e–h and 2p–w,
the resulting crude products were purified by silica gel column chromatography and
eluted by the mixture of petroleum ether (60–90 ꢀC) and ethyl acetate from 4:1 to 1:1
(by volume). For the others, crude products were recrystallized from anhydrous etha-
nol to give corresponding products. The purity of each synthesized compound was
checked by TLC at 254 nm, whose developer was the mixture of petroleum ether
(60–90 ꢀC) and ethyl acetate in the ratio of 2:1 (by volume).
3.4. Determination of crystal structure of compound 2r
The pure sample of 2r was dissolved in anhydrous ethanol and heated under reflux
for 1 h. The solution obtained was placed at room temperature for four days. The yel-
low prismatic single crystal was obtained. A suitable crystal was selected and mounted
on a Xcalibur, Eos diffractometer. The crystal was kept at 293.15 K during data collec-
tion. Using Olex2 (Dolomanov et al. 2009), the structure was solved with the Superflip
(Palatinus and Chapuis 2007) structure solution program using Charge Flipping and
refined with the ShelXL (Sheldrick 2008) refinement package using Least Squares
minimisation.
3.5. Assay of insecticidal activity
The insecticidal activity of the target compounds against L. separata and P. rapae was
determined according to the literatures (Tang et al. 2011; Tang and Hou 2011).
3.5.1. Assay of L. separata
The tested compounds and beta-cypermethrin (purity 95%) were dissolved in DMSO,
respectively. The solution obtained was diluted into five different concentrations with
0.1% Tween-80 distilled water. Maize leaves were cut into strips (2 cm ꢃ 5 cm) and
dipped in the solutions for 5 s. The leaves were allowed to air-dry and placed in Petri
dishes (9 cm). Ten third-instar larvae of L. separata were put into one Petri dish. The
Petri dishes were placed in the laboratory held at 22–24 ꢀC, 60% RH and 14:10 h light:
dark photoperiod. Control groups were treated with the corresponding solutions with-
out the tested compound or beta-cypermethrin. The experiment for each concentra-
tion was replicated three times. Mortality was recorded 24 h after treatment.
Percentage mortality was corrected according to the formula of Abbott and LC50

NATURAL PRODUCT RESEARCH
7
values were calculated with the Statistics Package for the Social Sciences (SPSS) based
on probit analysis.
3.5.2. Assay of P. rapae
The tested compounds and beta-cypermethrin (purity 95%) were dissolved in DMSO,
respectively. The solution obtained was diluted into five different concentrations with
0.1% Tween-80 distilled water. Twenty third-instar larvae of P. rapae were selected
from cabbage leaves. They were dipped in the solutions for 5 s within a small cage.
They were placed on filter paper to absorb the surplus solutions. Then, they were
transferred into Petri dishes (15 cm) with fresh cabbage leaves. The Petri dishes were
placed in the laboratory held at 24–26 ꢀC, 75–95% RH and 12:12 h light: dark photo-
period. Control groups were treated with the corresponding solutions without the
tested compound or beta-cypermethrin. The experiment for each concentration was
replicated three times. The following procedures were the same as the assay of
L. separata.
4. Conclusion
Thirty semicarbazone and thiosemicarbazone derivatives from chalcones were
designed and synthesized. The molecular structure of 2r was determined by single
crystal X-ray diffraction. Their insecticidal activity was evaluated against the above two
pests. 2d–h, 2n, 2p–s, 4e and 4d showed good insecticidal activity against one or two
of the two pests. In particular, 2e–g had the best insecticidal effects and their activity
against the two pests even surpassed beta-cypermethrin. Similarly, the activity of 2p
against P. rapae was superior to beta-cypermethrin. Some interesting results have
been obtained in respect to the relationship between structure and activity.
Additionally, 2e–g and 2p can be further used as lead compounds to design and syn-
thesize more analogues because they have simple structure and excellent insecti-
cidal activity.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
This study was supported by the Technical Innovation Programs of Chengdu Municipal Bureau
of Science and Technology (Project No. 2018-YF05-00970-SN), the Innovation Fund of
Postgraduate of Xihua University (Project No. YCJJ2019025) and the Undergraduate Innovation
and Entrepreneurship Training Programs of Xihua University (Project No. 201810623009).
References
Alam O, Mullick P, Verma SP, Gilani SJ, Khan SA, Siddiqui N, Ahsan W. 2010. Synthesis, anticon-
vulsant and toxicity screening of newer pyrimidine semicarbazone derivatives. Eur J Med
Chem. 45(6):2467–2472.

8
W. CHENG ET AL.
Aly MM, Mohamed YA, El-Bayouki KAM, Basyouni WM, Abbas SY. 2010. Synthesis of some new
4(3H)-quinazolinone-2-carboxaldehyde thiosemicarbazones and their metal complexes and a
study on their anticonvulsant, analgesic, cytotoxic and antimicrobial activities – Part-1. Eur J
Med Chem. 45(8):3365–3373.
Cao S, Qian X, Song G, Huang Q. 2002. Syntheses and insecticidal activity of new 2-(5-(trifluoro-
methyl)pyridyloxymethyl)-1,3,4-oxadiazoles. J Fluor Chem. 117(1):63–66.
Chen L, Wang X, Lu T, Hou T. 2007. Lead optimization and insecticidal activity of analogues of
daphneolone isolated from Stellera chamaejasme L. Pest Manag Sci. 63(9):928–934.
Di X, Liu Y, Liu Y, Yu X, Xiao H, Tian X, Gao R. 2007. Synthesis and insecticidal activities of pyri-
dine ring derivatives of podophyllotoxin. Pestic Biochem Phys. 89(1):81–87.
Dolomanov OV, Bourhis LJ, Gildea RJ, Howard JAK, Puschmann H. 2009. Olex2: a complete struc-
ture solution, refinement and analysis program. J Appl Crystallogr. 42(2):339–341.
Gan C, Cui J, Su S, Lin Q, Jia L, Fan L, Huang Y. 2014. Synthesis and antiproliferative activity of
some steroidal thiosemicarbazones, semicarbazones and hydrozones. Steroids. 87:99–107.
Gao P, Hou TP, Gao R, Cui Q, Liu SG. 2001. Activity of the botanical aphicides 1,5-diphenyl-1-
pentanone and 1,5-diphenyl-2-penten-1-one on two species of Aphididnae. Pest Manag Sci.
57(3):307–310.
Hou T, Ciu Q, Chen S, Hou R, Liu S. 2002. New compounds against aphides from Stellera
chamaejasme L. Chin J Org Chem. 22:67–70.
Liu YQ, Liu Y, Xiao H, Gao R, Tian X. 2008. Synthesis and insecticidal activities of novel
derivatives of podophyllotoxin: Part XII. Pestic Biochem Phys. 91(2):116–121.
Liu Z, Wu S, Wang Y, Li R, Wang J, Wang L, Zhao Y, Gong P. 2014. Design, synthesis and
biological evaluation of novel thieno[3,2-d] pyrimidine derivatives possessing diaryl semicar-
bazone scaffolds as potent antitumor agents. Eur J Med Chem. 87:782–793.
Palatinus L, Chapuis G. 2007. Superflip – a computer program for the solution of crystal struc-
tures by charge flipping in arbitrary dimensions. J Appl Crystallogr. 40(4):786–790.
Peng LN, Lin RS, Zeng J. 1996. Determination of the insecticidal resistance of Pieris rapae. J
North West Agric Univ. 18:530–532.
Qian Y, Zhang HJ, Lv PC, Zhu HL. 2010. Synthesis, molecular modeling and biological
evaluation of guanidine derivatives as novel antitubulin agents. Bioorg Med Chem. 18(23):
8218–8225.
Salgado VL, Hayashi JH. 2007. Metaflumizone is a novel sodium channel blocker insecticide. Vet
Parasitol. 150(3):182–189.
Sheldrick GM. 2008. A short history of Shelx. Acta Crystallogr A: Found Crystallogr. 64(1):
112–122. A
Tang XR, Chen S, Wang L. 2011. Purification and identification of carvacrol from the root of
Stellera chamaejasme and research on its insecticidal activity. Nat Prod Res. 25(3):320–325.
Tang XR, Hou TP. 2011. Isolation and identification of 2-isopropyl-5-methylphenol from Stellera
chamaejasme and its insecticidal activity against Aphis craccivora and Pieris rapae. Nat Prod
Res. 25(4):381–386.
Tang XR, Yang J, Gao S, Liu H, Gao Y, Xu ZH, Zeng Y, Zhang Y, Du Q, Wang L, Xihua University.
2016 Mar 30. Semicarbazone analogues and their preparation methods and applications.
Chinese patent CN105439995A.
Tang XR, Yang J, Gao S, Liu H, Gao Y, Zhang Y, Xu ZH, Zeng Y, Li WY, Wang L, Xihua University.
2016 Apr 6. 1-(2-Furyl)-1,3-piperylene analogues and their preparation methods and applica-
tions. Chinese patent CN105461670A.
Tao L, Lin C, Hou T. 2007. Synthesis and structure–activity study of botanical aphicides 1,5-
diphenyl-1-pentanone analogues. Pestic Biochem Phys. 89(1):60–64.
Xu X, Qian X, Li Z, Huang Q, Chen G. 2003. Synthesis and insecticidal activity of new substituted
N-aryl-N0-benzoylthiourea compounds. J Fluor Chem. 121(1):51–54.
Xue CB, Zhang L, Luo WC, Xie XY, Jiang L, Xiao T. 2007. 3D-QSAR and molecular docking studies
of benzaldehyde thiosemicarbazone, benzaldehyde, benzoic acid, and their derivatives as
phenoloxidase inhibitors. Bioorg Med Chem. 15(5):2006–2015.

NATURAL PRODUCT RESEARCH
9
Yang CL, Gong GJ, Tan FJ, You ZP. 1995. Studies on resistance and mode of action of Leucania
separata. Plant Prot. 21:2–5.
Zhang HJ, Qia Y, Zhu DD, Yang XG, Zhu HL. 2011. Synthesis, molecular modeling and biological
evaluation of chalcone thiosemicarbazide derivatives as novel anticancer agents. Eur J Med
Chem. 46(9):4702–4708.
Zheng X, Li Z, Wang Y, Chen W, Huang Q, Liu C, Song G. 2003. Syntheses and insecticidal activ-
ities of novel 2,5-disubstituted 1,3,4-oxadiazoles. J Fluor Chem. 123(2):163–169.