Synthesis and Crystal Structure of Chalcone Derivatives and Their Effect on α-Glucosidase

Article abstract of DOI:10.1007/s10870-020-00842-5

Abstract: Five chalcone derivatives (E)-1-(2-(2-bromoethoxy)phenyl)-3-phenylprop-2-en-1-one(1), (E)-1-(2-(3-bromopropoxy)phenyl)-3-phenylprop-2-en-1-one(2),(E)-1-(2-(4-bromopropoxy)phenyl)-3-phenylprop-2-en-1-one(3),(E)-1-(2-(5-bromopropoxy)phenyl)-3-phenylprop-2-en-1-one(4),(E)-1-(2-(6-bromopropoxy)phenyl)-3-phenylprop-2-en-1-one(5) were synthesized and characterized by ¹H NMR, HRMS. The crystalline structures of compounds 4 and 5 were further characterized by X-ray crystal diffraction. Among the five compounds, 1 and 2 showed inhibitory activity on α-glucosidase, but 4 and 5 increased the activity of α-glucosidase. Graphic Abstract: Five chalcone derivatives were synthesized and characterized by ¹H MNR and HRMS. The crystalline structures of two compounds were further characterized by X-ray crystal diffraction. Two of the compounds have the ability to inhibit α-glucosidase, and two different compounds have the ability to promote α-glucosidase. [Figure not available: see fulltext.].

Full text of DOI:10.1007/s10870-020-00842-5

Journal of Chemical Crystallography
https://doi.org/10.1007/s10870-020-00842-5
ORIGINAL PAPER
Synthesis and Crystal Structure of Chalcone Derivatives and Their
Efect on α‑Glucosidase
Ping Lin1 · Zhong‑Ping Yin1 · Meng Wang1 · Jia Liu1 · En Yuan3 · Da‑Yong Peng1,2 · Xu‑Liang Nie1,2
Xin‑Chen Shang‑Guan1
·
Received: 13 December 2018 / Accepted: 20 June 2020
© Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
Five chalcone derivatives (E)-1-(2-(2-bromoethoxy)phenyl)-3-phenylprop-2-en-1-one(1), (E)-1-(2-(3-bromopropoxy)phenyl)-
3-phenylprop-2-en-1-one(2),(E)-1-(2-(4-bromopropoxy)phenyl)-3-phenylprop-2-en-1-one(3),(E)-1-(2-(5-bromopropoxy)
phenyl)-3-phenylprop-2-en-1-one(4),(E)-1-(2-(6-bromopropoxy)phenyl)-3-phenylprop-2-en-1-one(5) were synthesized and
characterized by 1H NMR, HRMS. The crystalline structures of compounds 4 and 5 were further characterized by X-ray
crystal difraction. Among the fve compounds, 1 and 2 showed inhibitory activity on α-glucosidase, but 4 and 5 increased
the activity of α-glucosidase.
Graphic Abstract
Five chalcone derivatives were synthesized and characterized by 1H MNR and HRMS. The crystalline structures of two
compounds were further characterized by X-ray crystal difraction. Two of the compounds have the ability to inhibit
α-glucosidase, and two diferent compounds have the ability to promote α-glucosidase.
Keywords Chalcone derivatives · Synthesis · Crystal structure · α-Glucosidase
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10870-020-00842-5) contains
Introduction
supplementary material, which is available to authorized users.
Chalcones are natural organic compounds, widely found in
plants, with applications in a variety of scientifc domains,
such as non-linear optics[1], the manufacture of dyes [2] and
in supramolecular chemistry [3]. Additionally, various deriv-
atives of chalcones have shown promise in pharmaceutical
applications. Because of their privileged structures, they
may display anti-diabetes [4, 5], anti-cancer [6], anti-malar-
ial [7, 8], anti-bacterial [9, 10], anti-viral [11, 12], anti-HIV
[13, 14], or anti-infammatory activity [15]. Applications
depend on the structural features, like planarity, electronic
delocalization and substitution pattern on the aromatic rings
* Da-Yong Peng
dayongpeng@163.com
* Xu-Liang Nie
13576953044@163.com
1
Jiangxi Key Laboratory of Natural Products and Functional
Foods, Jiangxi Agricultural University, Nanchang 330045,
China
2
College of Science, Jiangxi Agricultural University,
Nanchang 330045, China
3
College of Pharmacy, Jiangxi University of Traditional
Chinese Medicine, Nanchang 330004, China
Vol.:(0123456789)
1 3

Journal of Chemical Crystallography
[16]. Thus, considering the potential pharmaceutical actives
of the chalcone structural system, the modifcation of the
privileged structure is an interesting goal. Toward this end,
many studies have recently been carried out [17–19]. For
example, chalcone derivatives were identifed as potential
α-glucosidase inhibitors [20].
(EC3.2.1.20) and 4-Nitrophenyl-α-d-gluocpynoaside
(PNPG) were obtained from Sigma. Other reactants of AR
grade were obtained commercially and used without further
purifcation.1H NMR analyses were performed on a Varian
VNMR 400 MHz. The X-ray crystal structure data were col-
lected at room temperature on a Bruker APEX II area detec-
tor difractometer equipped with a graphite-monochromator,
using MoKα radiation (λ= 0.71073 Å) and ψ–ω scan mode
(Scheme 1).
Numerous studies reported on modifying chalcones with
methoxy, hydroxyl, and nitro groups. However, very few
investigations focus on chalcones with bromo side chains.
An example is the crystal structure and quantum chemical
investigation of chalcones with bromo butoxy side chains in
the para position [21] and a report on the synthesis, charac-
terization and crystal structure of fuoro-containing chalcone
derivatives [22]. In this paper, we report the synthesis of
a series of chalcones with bromo ethoxy, propoxy, butoxy,
pentoxy and hexyloxy side chains in the ortho-position, as
well as the crystal structures and the efects of these com-
pounds on α-glucosidase.
Synthesis of 2′‑Hydroxychalcone and 1–5
Synthesis of 2′‑Hydroxychalcone [22]
To a solution of equimolar amounts of 2’-hydroxyacetophe-
none and benzaldehyde in ethanol was added an aqueous
solution of 4 M NaOH. The mixture was stirred for 2–8
h at 0 °C. The reaction mixture was neutralized with 6 M
HCl and pH adjusted to 2. The mixture was then extracted
with ethyl acetate, washed with water and saturated brine.
It was further purifed by either recrystallization or column
Experimental
1
chromatography to yield the pure compound. H NMR
Materials and Measurements
(400 MHz, DMSO-d6) δ 12.53 (s, 1H), 8.29–8.22 (m, 1H),
8.06–7.99 (m, 1H), 7.92–7.87 (m, 2H), 7.87–7.80 (m, 1H),
7.59–7.51 (m, 1H), 7.49–7.41 (m, 3H), 7.04 – 6.96 (m,
2H). 13C NMR (100 MHz, DMSO-d6) δ 193.58, 161.90,
The synthesis of 2’-hydroxychalcone was performed
according to literature procedures [22]. α-Glucosidase
Scheme 1 Synthesis and struc-
ture of chalcone derivatives
1 3

Journal of Chemical Crystallography
144.74, 136.26, 134.41, 130.88, 130.83, 129.09, 128.89,
121.68, 120.68, 119.10, 117.70. HRMS (ESI) m/z: calcd for
C15H12O2 for [M+1]+, calculated 225.0837, found 225.0883.
135.13, 133.70, 130.85, 130.17, 129.42, 129.34, 128.84,
127.76, 121.01, 113.51, 68.42, 35.00, 32.43, 28.39, 24.89.
HRMS (ESI) m/z: calcd for C20H21BrO2 [M+H]+ 372.0798,
found 372.0796.
Synthesis of 1–5
Compound 5: pale yellow crystals; yield: 75%. m.p. 74–76
℃. 1H NMR (500 MHz, DMSO) δ 7.77–7.67 (m, 2H), 7.53 (s,
1H), 7.52–7.50 (m, 2H), 7.49 (s, 1H), 7.46–7.42 (m, 3H), 7.17
(d, J=8.1 Hz, 1H), 7.08–7.03 (m, 1H), 4.09 (t, J=6.0 Hz, 2H),
3.35 (t, J=6.8 Hz, 2H), 1.73–1.65 (m, 2H), 1.60–1.53 (m, 2H),
1.40–1.32 (m, 2H), 1.33–1.23 (m, 2H). 13C NMR (125 MHz,
DMSO) δ 192.46, 157.84, 142.21, 135.12, 133.71, 130.87,
130.19, 129.43, 129.31, 128.83, 127.73, 120.98, 113.46, 68.50,
35.29, 32.47, 29.11, 27.77, 25.33. HRMS (ESI) m/z: calcd for
C21H23BrO2 [M+Na]+ 408.0773, found 408.0780.
1,2-Dibromoethane (8.2 g, 40.5 mmol) was added dropwise
to a solution of 2′-hydroxychalcone (2 g, 13.5 mmol) and
K2CO3(3.7 g, 27 mmol) in acetone (50 mL) at room tem-
perature. The reaction mixture was stirred for 4–5 h. Com-
pletion of reaction was monitored by TLC analysis. After
completion of the reaction, the product was extracted with
ethyl acetate (3 × 50 mL) and dried with anhydrous Na2SO4.
The product was then separated by silica gel column chro-
matography to obtain compound 1 as pale-yellow oil with a
yield of 80%. 1H NMR (500 MHz, DMSO) δ 7.79–7.74 (m,
2H), 7.63–7.59 (m, 2H), 7.59–7.56 (m, 1H), 7.55–7.52 (m,
1H), 7.46–7.40 (m, 3H), 7.19 (d, J = 8.4 Hz, 1H), 7.13–7.07
(m, 1H), 4.50–4.45 (m, 2H), 3.83–3.79 (m, 2H). 13C NMR
(125 MHz, DMSO) δ 191.96, 156.95, 142.69, 135.13,
133.78, 130.86, 130.51, 129.39, 129.35, 129.08, 127.43,
121.61, 113.66, 68.95, 31.73. HRMS (ESI) m/z: calcd for
C17H15BrO2 [M + H]+ 330.0255, found 330.0257.
Structure Determination
The crystal data for 4 and 5 were integrated using the pro-
gram SAINT and corrected for absorption efects using the
program SADABS [23]. The structures were solved by direct
methods and refned on F2by full-matrix least squares using
SHELXTL-2014 software [24]. All non-hydrogen atoms were
located by direct methods and subsequent diference Fourier
syntheses. The hydrogen atoms bound to carbon were placed
in calculated positions and refined using a riding model.
Crystallographic data and refnement information are given
in Table 1.
Compounds 2, 3, 4, and 5 were synthesized following the
procedure described for 1. Pale yellow crystals of 4 and 5,
suitable for X-ray difraction analysis, were obtained from
ethyl acetate and acetone (V/V=1:1) with yields of 80 % and
75%, respectively.
1
Compound 2: pale yellow oil; yield: 83%. H NMR
In Vitro α‑Glucosidase Inhibitory Activity Study
(500 MHz, DMSO) δ 7.77–7.70 (m, 2H), 7.56–7.51 (m,
3H), 7.46 (s, 1H), 7.45–7.42 (m, 3H), 7.20 (d, J=8.2 Hz,
1H), 7.11–7.05 (m, 1H), 4.20 (t, J = 5.8 Hz, 2H), 3.56 (t,
J=6.7 Hz, 2H), 2.29–2.19 (m, 2H). 13C NMR (125 MHz,
DMSO) δ 192.46, 157.30, 142.71, 134.96, 133.63, 130.95,
130.17, 129.46, 129.44, 128.92, 127.43, 121.27, 113.49,
66.46, 32.31, 31.47. HRMS (ESI) m/z: calcd for C18H17BrO2
[M+H]+ 344.0485, found 344.0482.
The inhibition activity of these compounds on α-glucosidase
activity was evaluated using a micro determination model
based on the reaction of α-glucosidase and 4-nitrophenyl-α-d-
gluocpynoaside (PNPG). The test compounds were dissolved
in DMSO and phosphate bufer (PB) to prepare the required
distributing (10, 20 mmol/L) concentration. Specifcally,
α-glucosidase from Saccharomyces cerevisiae was assayed
using a 0.01 M phosphate bufer at pH 6.8 and 10 mM PNPG
as the substrate. The concentration of the enzymes was 1 U/
mL in each experiment. PB (160 μL), various concentrations
of the derivatives (10 μL), and α-glucosidase (10 μL) were
added to 96-well polystyrene plates, and the plates were incu-
bated at 37 °C for 20 min. After 20 min preincubation, 20 μL
of PNPG solution were added to the mixture. The reaction was
carried out at 37 °C for 10 min. The absorbance was measured
at 405 nm using a multiscanner. Acarbose was used as the
positive control in this study. The percentage of enzyme inhibi-
tion was determined by the following equation:
1
Compound 3: pale yellow oil; yield: 85%. H NMR
(500 MHz, DMSO) δ 7.76–7.69 (m, 2H), 7.54 (s, 1H),
7.53–7.50 (m, 2H), 7.49 (s, 1H), 7.46–7.43 (m, 3H), 7.19
(d, J=8.1 Hz, 1H), 7.10–7.01 (m, 1H), 4.13 (t, J=6.0 Hz,
2H), 3.42 (t, J=6.5 Hz, 2H), 1.94–1.87 (m, 2H), 1.86–1.79
(m, 2H). 13C NMR (125 MHz, DMSO), 157.65, 142.41,
135.06, 133.66, 130.88, 130.17, 129.45, 129.35δ 192.42,
128.89, 127.62, 121.06, 113.52, 67.73, 34.97, 29.50, 27.93.
HRMS (ESI) m/z: calcd for C19H19BrO2 [M+H]+ 358.0641,
found 358.0640.
Compound 4: pale yellow crystals; yield: 80%; m.p. 58–60
℃; 1H NMR (500 MHz, DMSO) δ 7.76–7.69 (m, 2H), 7.53
(s, 1H), 7.52–7.50 (m, 2H), 7.49 (s, 1H), 7.47–7.41 (m, 3H),
7.18 (d, J=8.2 Hz, 1H), 7.09–7.03 (m, 1H), 4.10 (t, J=5.8,
2H), 3.33 (t, J=5.3 Hz, 2H), 1.76–1.65 (m, 4H), 1.50–1.41 (m,
2H). 13C NMR (125 MHz, DMSO) δ 192.49, 157.79, 142.23,
(
)
Inhibition(%) = ΔAcontrol − ΔAsample ∕ΔAcontrol × 100
1 3

Journal of Chemical Crystallography
Table 1 Crystal and structure
refnement data of 4 and 5
4
5
Empirical formula
CCDC deposition number
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
C20H21BrO2
1,872,372
373.27
296(2)
0.71073
Triclinic
P-1
C21H23BrO2
1,872,371
387.29
296(2)
0.71073
Monoclinic
P21/c
a (Å)
b(Å)
8.297(7)
8.756(8)
8.3077(15)
8.4018(15)
c(Å)
α(°)
β(°)
13.007(11)
90.046(11)
106.892(10)
99.507(11)
890.5(13)
2
26.690(5)
90
91.324(2)
90
1862.5(6)
4
γ(°)
V(Å3)
Z
Dc (g cm-3)
Mu(MoKa) (mm)
F(000)
1.392
2.315
384
1.381
2.217
800
Crystal size (mm)
Θ range for date collection (°)
Refections collected
Independent refection
Goodness-of-ft on F2
Final R indices [I>2σ(I)]a, b
R indices (all data)a
0.20×0.18×0.16
2.605–25.497
6587
3262 [Rint =0.019]
1.005
R1 =0.0779, wR2 =0.1895
R1 =0.1067, wR2 =0.2147
0.20×0.20×0.16
2.54–24.99
13,975
3459 [Rint =0.0181]
1.025
R1 =0.0359, wR2 =0.0726
R1 =0.0545, wR2 =0.0803
aR1= Σ║Fo│ − │Fc║/ Σ│Fo│
2
bwR2 =[Σw(Fo2 − Fc )2/ Σw(Fo2)2]1/2
Results and Discussion
Crystal Structure of 4 and 5
X-ray difraction analysis shows that compound 4 crystallizes
in the triclinic space group P-1. The molecule is shown in
the Fig. 1, and the observed bond lengths and angles are very
similar to those reported in the literature for chalcone deriva-
tives [24]. The dihedral angle between the phenyl groups is
71.61(18)º, which is larger than that reported in the litera-
ture for 3-cinnamoyl-4-hydroxybenzoic acid [25], because
of the alkoxyl substituents in the ortho-position. The torsion
angles of C3–C2–C7–O2, C3–C2–C7–C8, C2–C7–C8–C9,
C7–C8–C9–C10, C2–C1–O1–C16, C1–O1–C16–C17,
O1–C16–C17–C18,C16–C17–C18–C19,C17–C18–C19–C20and
C18–C19–C20–Br are 25.413(740)°, − 153.152(512)°,−148
.287(517)°, 178.107(490)°, − 167.363(462)°, 160.445(454)°,
65.284(621)°, 178.329(506)°, 179.273(548)° and
79.096(667)°, respectively.
Fig. 1 Crystal structure of 4 with 30% displacement ellipsoids
with those reported in the literature for chalcone deriva-
tives [26]. The dihedral angle between the phenyl groups
is 56.12(9)º. The Br1–C21–C20–C19 torsion angle in
structure 5 is 178.78(16)º and Br is in a trans position,
whereas the B1–C20–C19–C18 torsion angle in structure
4 is 67.1(6)º and Br is in a gauche conformation.
Compound 5 crystallizes in the monoclinic space
group P21/c. In the molecule of 5 (shown in the Fig. 2),
bond lengths and angles are unexceptional and agree well
1 3

Journal of Chemical Crystallography
Table 2 α-Glucosidase inhibition ratio at diferent concentrations
(mmol/L)
Compd
Structure
Inhibition ratio (%)
10 mmol/L
9.22
20 mmol/L
1
15.75
10.44
2.11
2
3
5.28
−
Fig. 2 Crystal structure of 5 with 30% displacement ellipsoids
We tried but failed to crystallize the oils we obtained for
compound 1, 2 and 3 using the same methods there were
successful for compound 4 and 5. Likely, the shorter side
chains in are responsible for this behavior.
4
5
−10.60
−4.08
−14.39
−10.42
In Vitro α‑Glucosidase Inhibitory Activity
In order to explore the synergistic biological potential of
the synthesized molecules, they were subjected to in vitro
α-glucosidase inhibition using the same concentrations (10
mmol/L, 20 mmol/L) for all experiments Table 2. Com-
pounds 1, 2 and 3 exhibited inhibition activities and may
have the potential in preventing the rise of postprandial glu-
cose levels in diabetics. Compounds 4 and 5, however, are
not inhibiting α-glucosidase. Yet, our results indicate that the
length of the side chain has a large impact on α-glucosidase
inhibition. The side chain length infuenced the activity
of α-glucosidase had been reported previously [27].The
1-deoxynojirimycin (1-DNJ) with N-alkyl chain of various
length showed diferent inhibition efect [28]. Addition, a
class of α-glucosidase inhibitors were synthesized based on
iminofuranosides with various alkyl groups substituted at
the anomeric position. These compounds showed a strong
correlation between chain length and inhibition activities,
neither short nor long chain length showed less activity
[29]. Our results are similar with previous studies. Since
all compounds showed less than 50% inhibition, we did not
further evaluate them for half maximal inhibitory concentra-
tion (IC50).
Acarbose
2′-Hydroxychalcone
38.33
2.79
49.32
5.32
ccdc.cam.ac.uk) or also available from the author Xu-Liang
Nie.
Acknowledgements This work was supported by The National Nat-
ural Science Foundation of China (No. 31460436, 31260368), Sci-
entifc Research Project of Jiangxi Food and Drug Administration
(No.2017sp28). The Research Foundation of Educational Department
of Jiangxi Province [No. GJJ160382]. X-ray data were collected at
Instrumental Analysis Center Nanchang Hang Kong University, Nan-
chang, 330063, People’s Republic of China.
References
1. Maragatham G, Selvarani S, Rajakumar P, Lakshmi S (2018)
Structure determination and quantum chemical analysis of chal-
cone derivatives. J Mol Struct. https://doi.org/10.1016/j.molst
ruc.2018.11.048
Supplementary Data
2. Teo KY, Tiong MH, Wee HY, Jasin N, Liu Z-Q, Shiu MY, Tang
JY, Tsai J-K, Rahamathullah R, Khairul WM, Tay MG (2017) The
infuence of the push-pull efect and a π-conjugated system in con-
version efciency of bis-chalcone compounds in a dye sensitized
solar cell. J Mol Struct 1143:42–48. https://doi.org/10.1016/j.
molstruc.2017.04.059
Supplementary data CCDC Numbers 1872371 and 1872372
contain the supplementary crystallographic data for the
structures reported in this paper. Copies of this information
may be obtained free of charge from the Director, CCDC,
12 Union Road, Cambridge CB2 1EZ, UK (Fax: (+44)1223
336-033; e-mail: deposit@ccdc.cam.ac.uk or https://www.
3. Low JN, Cobo J, Nogueras M, Sánchez A, Albornoz A, Abonia
R (2002) A comparison of the supramolecular structures of
1-(6-amino-1,3-benzodioxol-5-yl)-3-(3,4,5-trimethoxyphenyl)
1 3

Journal of Chemical Crystallography
heterocyclic chalcones. Chem Data Collect. https://doi.
org/10.1016/j.cdc.2017.04.004
prop-2-en-1-one and 1-(6-amino-1,3-benzodioxol-5-yl)-3-[4-(N,
N-dimethylamino)phenyl]prop-2-en-1-one. Acta Crystallogr C
58(Pt 1):42–45. https://doi.org/10.1107/s0108270101018297
4. Bak EJ, Hong GP, Lee CH, Lee TI, Woo GH (2011) Efects
of novel chalcone derivatives on α-glucosidase, dipeptidyl
peptidase-4, and adipocyte diferentiation in vitro. BMB Rep
44(6):410–414. https://doi.org/10.5483/BMBRep.2011.44.6.410
5. Singh P, Anand A, Kumar V (2014) Recent developments in bio-
logical activities of chalcones: a mini review. Eur J Med Chem
85(45):758–777. https://doi.org/10.1002/chin.201445285
6. Mayur YCGJP, RajendraPrasad VVS, Lemos C, Sathish NK
(2009) Design of new drug molecules to be used in reversing
multidrug resistance in cancer cells. Curr Cancer Drug Targets
9(3):298–306. https://doi.org/10.2174/156800909788166619
7. Chen M, Theander TG, Christensen SB, Hviid L, Zhai L,
Kharazmi A (1994) Licochalcone A, a new antimalarial agent,
inhibits in vitro growth of the human malaria parasite Plasmodium
falciparum and protects mice from P yoelii infection. Antimicrob
Agents Chemother 38(7):1470–1475. https://doi.org/10.1128/
aac.38.7.1470
18. Barakat A, Al-Majid AM, Soliman SM, Islam MS, Ghawas HM,
Yousuf S, Choudhary MI, Wadood A (2017) Monoalkylated bar-
biturate derivatives: X-ray crystal structure, theoretical studies,
and biological activities. J Mol Struct 1141:624–633. https://doi.
org/10.1016/j.molstruc.2017.04.017
19. de Mello MVP, Abrahim-Vieira BA, Domingos TFS, de Jesus JB, de
Sousa ACC, Rodrigues CR, Souza AMT (2018) A comprehensive
review of chalcone derivatives as antileishmanial agents. Eur J Med
Chem 150:920–929. https://doi.org/10.1016/j.ejmech.2018.03.047
20. Sun H, Li Y, Zhang X, Lei Y, Ding W, Zhao X, Wang H, Song
X, Yao Q, Zhang Y, Ma Y, Wang R, Zhu T, Yu P (2015) Syn-
thesis, α-glucosidase inhibitory and molecular docking studies
of prenylated and geranylated favones, isofavones and chal-
cones. Bioorg Med Chem Lett 25(20):4567–4571. https://doi.
org/10.1016/j.bmcl.2015.08.059
21. Maragatham G, Selvarani S, Rajakumar P, Lakshmi S (2017)
Crystal structures of three 1-[4-(4-bromo-but-oxy)-phen-yl]
chalcone derivatives: (E)-1-[4-(4-bromo-but-oxy)-phen-yl]-3-
phenyl-prop-2-en-1-one, (E)-1-[4-(4-bromo-but-oxy)-phen-yl]-
3-(4-meth-oxy-phen-yl)prop-2-en-1-one and (E)-1-[4-(4-bromo-
but-oxy)-phen-yl]-3-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one.
Acta Crystallogr E Crystallogr Commun 73(Pt 8):1232–1236.
https://doi.org/10.1107/s2056989017010052
8. Yadav N, Dixit SK, Bhattacharya A, Mishra LC, Sharma M,
Awasthi SK, Bhasin VK (2012) Antimalarial activity of newly
synthesized chalcone derivatives in vitro. Chem Biol Drug Des
80(2):340–347. https://doi.org/10.1111/j.1747-0285.2012.01383
.x
22. Karki R, Jun KY, Kadayat TM, Shin S, Thapa Magar TB, Bist
G, Shrestha A, Na Y, Kwon Y, Lee ES (2016) A new series of
2-phenol-4-aryl-6-chlorophenyl pyridine derivatives as dual
topoisomerase I/II inhibitors: synthesis, biological evaluation
and 3D-QSAR study. Eur J Med Chem 113:228–245. https://doi.
org/10.1016/j.ejmech.2016.02.050
9. Choi D, Park JC, Lee HN, Moon JH, Ahn HW, Park K, Hong J
(2018) In vitro osteogenic diferentiation and antibacterial poten-
tials of chalcone derivatives. Mol Pharm 15(8):3197–3204. https
://doi.org/10.1021/acs.molpharmaceut.8b00288
10. Shakhatreh MA, Al-Smadi ML, Khabour OF, Shuaibu FA,
Hussein EI, Alzoubi KH (2016) Study of the antibacterial and
antifungal activities of synthetic benzyl bromides, ketones,
and corresponding chalcone derivatives. Drug Des Devel Ther
10:3653–3660. https://doi.org/10.2147/dddt.S116312
23. Bruker (2005) APEX2, SAINT and SADABS. Bruker AXS Inc,
Madison
24. Song Z, Kwok RT, Zhao E, He Z, Hong Y, Lam JW, Liu B, Tang
BZ (2014) A ratiometric fuorescent probe based on ESIPT and
AIE processes for alkaline phosphatase activity assay and visu-
alization in living cells. ACS Appl Mater Interfaces 6(19):17245–
17254. https://doi.org/10.1021/am505150d
11. Herencia F, Ferrándiz ML, Ubeda A, Guillén I, Dominguez JN,
Charris JE, Lobo GM, Alcaraz MJ (1999) Novel anti-infamma-
tory chalcone derivatives inhibit the induction of nitric oxide syn-
thase and cyclooxygenase-2 in mouse peritoneal macrophages.
FEBS Lett 453(1–2):129–134. https://doi.org/10.1016/s0014
-5793(99)00707-3
25. Chun-Mei G, Xiu-Ying S, Mi-Na W, Jia G, Xu-Liang N
(2020) Crystal structure of 3-cinnamoyl-4-hydroxybenzoic
acid, C
12. Jin YL, Jin XY, Jin F, Sohn DH, Kim HS (2008) Structure activ-
ity relationship studies of anti-infammatory TMMC derivatives:
4-dimethylamino group on the B ring responsible for lower-
ing the potency. Arch Pharm Res 31(9):1145–1152. https://doi.
org/10.1007/s12272-001-1281-7
16H12O4. Zeitschrift für Kristallographie. https://doi.
org/10.1515/ncrs-2020-0178
26. Sheldrick GM (2008) A short history of SHELX. Acta Crystallogr
A 64(Pt 1):112–122. https://doi.org/10.1107/s0108767307043930
27. Ghani U (2015) Re-exploring promising α-glucosidase inhibitors
for potential development into oral anti-diabetic drugs: fnding
needle in the haystack. Eur J Med Chem 103:133–162. https://
doi.org/10.1016/j.ejmech.2015.08.043
13. Sharma H, Patil S, Sanchez TW, Neamati N, Schinazi RF, Buola-
mwini JK (2011) Synthesis, biological evaluation and 3D-QSAR
studies of 3-keto salicylic acid chalcones and related amides as
novel HIV-1 integrase inhibitors. Bioorg Med Chem 19(6):2030–
2045. https://doi.org/10.1016/j.bmc.2011.01.047
28. Cendret V, Legigan T, Mingot A, Thibaudeau S, Adachi I, For-
cella M, Parenti P, Bertrand J, Becq F, Norez C, Désiré J, Kato A,
Blériot Y (2015) Synthetic deoxynojirimycin derivatives bearing
a thiolated, fuorinated or unsaturated N-alkyl chain: identifca-
tion of potent α-glucosidase and trehalase inhibitors as well as
F508del-CFTR correctors. Org Biomol Chem 13(43):10734–
10744. https://doi.org/10.1039/c5ob01526j
14. Uchiumi F, Hatano T, Ito H, Yoshida T, Tanuma S (2003) Tran-
scriptional suppression of the HIV promoter by natural com-
pounds. Antivir Res 58(1):89–98. https://doi.org/10.1016/s0166
-3542(02)00186-9
15. Liu Z, Tang L, Zou P, Zhang Y, Wang Z, Fang Q, Jiang L, Chen G,
Xu Z, Zhang H, Liang G (2014) Synthesis and biological evalu-
ation of allylated and prenylated mono-carbonyl analogs of cur-
cumin as anti-infammatory agents. Eur J Med Chem 74:671–682.
https://doi.org/10.1016/j.ejmech.2013.10.061
29. Natori Y, Imahori T, Murakami K, Yoshimura Y, Nakagawa S,
Kato A, Adachi I, Takahata H (2011) The synthesis and biological
evaluation of 1-C-alkyl-L-arabinoiminofuranoses, a novel class of
α-glucosidase inhibitors. Bioorg Med Chem Lett 21(2):738–741.
https://doi.org/10.1016/j.bmcl.2010.11.112
16. Lokesh BVS, Prasad YR, Shaik AB (2019) Synthesis, biological evalu-
ation and molecular docking studies of new pyrazolines as an antituber-
cular and cytotoxic agents. Infect Disord Drug Targets 19(3):310–321.
https://doi.org/10.2174/1871526519666181217120626
Publisher’s Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional afliations.
17. Ming LS, Jamalis J, Al-Maqtari HM, Rosli MM, Sankaranaray-
anan M, Chander S, Fun HK (2017) Synthesis, characterization,
antifungal activities and crystal structure of thiophene-based
1 3