Synthesis and evaluation of antitumour activity in vitro and in vivo of chrysin salicylate derivatives

Article abstract of DOI:10.1080/14786419.2017.1371159

A series of chrysin salicylate derivatives as potential antitumour agents were synthesised and evaluated their antitumour activities in vitro and in vivo. Most of the compounds exhibited moderate to good activities against MCF-7 cells, HepG2 cells, MGC-80

Full text of DOI:10.1080/14786419.2017.1371159

Natural Product Research
Formerly Natural Product Letters
ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: http://www.tandfonline.com/loi/gnpl20
Synthesis and evaluation of antitumour activity in
vitro and in vivo of chrysin salicylate derivatives
Xiangping Deng, Zihao Zhao, Shujuan Xiong, Runde Xiong, Juan Liu, Zhe
Wang, Liu Zou, Xiaoyong Lei, Xuan Cao, Zhizhong Xie, Yanming Chen, Xing
Zheng, Yunmei Liu & Guotao Tang
To cite this article: Xiangping Deng, Zihao Zhao, Shujuan Xiong, Runde Xiong, Juan Liu, Zhe
Wang, Liu Zou, Xiaoyong Lei, Xuan Cao, Zhizhong Xie, Yanming Chen, Xing Zheng, Yunmei Liu &
Guotao Tang (2017): Synthesis and evaluation of antitumour activity in vitro and in vivo of chrysin
salicylate derivatives, Natural Product Research, DOI: 10.1080/14786419.2017.1371159
To link to this article: http://dx.doi.org/10.1080/14786419.2017.1371159
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Date: 05 September 2017, At: 19:42

Natural Product research, 2017
ꢁꢁpꢂ://ꢃꢄi.ꢄꢅg/10.1080/14786419.2017.1371159
ꢀ
Synthesis and evaluation of antitumour activity in vitro and
in vivo of chrysin salicylate derivatives
a1
a,b1
a
a
a
Xiangping Deng , Zihao Zhao , Shujuan Xiong , Runde Xiong , Juan Liu ,
a
a
a
a
a
c
Zhe Wang , Liu Zou , Xiaoyong Lei , Xuan Cao , Zhizhong Xie , Yanming Chen ,
Xing Zheng , Yunmei Liu and Guotao Tang
a
a
a
ꢆ
hꢇnꢆn Pꢅꢄvinꢈꢉ cꢄꢄpꢉꢅꢆꢁivꢉ Innꢄvꢆꢁiꢄn cꢉnꢁꢉꢅ fꢄꢅ Mꢄꢊꢉꢈꢇꢊꢆꢅ tꢆꢅgꢉꢁ Nꢉw dꢅꢇg sꢁꢇꢃy, Inꢂꢁiꢁꢇꢁꢉ ꢄf Pꢀꢆꢅmꢆꢈy
b
ꢆnꢃ Pꢀꢆꢅmꢆꢈꢄꢊꢄgy, univꢉꢅꢂiꢁy ꢄf sꢄꢇꢁꢀ cꢀinꢆ, hꢉngyꢆng, cꢀinꢆ; Pꢀꢆꢅmꢆꢈy dꢉpꢆꢅꢁmꢉnꢁ, Xiꢆngꢁꢆn cꢉnꢁꢅꢆꢊ
hꢄꢂpiꢁꢆꢊ, Xiꢆngꢁꢆn, cꢀinꢆ; Mꢇ dꢆn Jiꢆng Yꢄꢇ Bꢄ Pꢀꢆꢅmꢆꢈꢉꢅꢁiꢈꢆꢊ cꢄ.lꢁꢃ, Mꢇꢃꢆnjiꢆng, cꢀinꢆ
ꢈ
ABSTRACT
ARTICLE HISTORY
rꢉꢈꢉivꢉꢃ 19 Mꢆy 2017
aꢈꢈꢉpꢁꢉꢃ 9 aꢇgꢇꢂꢁ 2017
A series of chrysin salicylate derivatives as potential antitumour
agents were synthesised and evaluated their antitumour activities
in vitro and in vivo. Most of the compounds exhibited moderate to
good activities against MCF-7 cells, HepG2 cells, MGC-803cells and
MFC cells. Among them, compound 3f showed the most potent
activity against MGC-803 cells and MFC cells with IC50 values of
KEYWORDS
cꢀꢅyꢂin; ꢂꢆꢊiꢈyꢊꢆꢁꢉ
ꢃꢉꢅivꢆꢁivꢉꢂ; ꢂynꢁꢀꢉꢂiꢂ;
ꢆnꢁiꢁꢇmꢄꢇꢅ
2
3.83 ± 3.68 and 27.34 ± 5.21 μM, respectively. The flow cytometry
assay reconfirmed that compound 3f promoted the occurrence of
tumour cells’ G1/S block under the inhibiting effect of compound
3
f. Compound 3f possessed higher antitumour efficacy in tumour-
bearing mice, compared with the positive control 5-Fu and the blank
control saline.
CONTACT Gꢇꢄꢁꢆꢄ tꢆng
tꢀꢉꢂꢉ ꢆꢇꢁꢀꢄꢅꢂ ꢈꢄnꢁꢅibꢇꢁꢉꢃ ꢉqꢇꢆꢊꢊy ꢁꢄ ꢁꢀiꢂ wꢄꢅk.
ꢁgꢁzq@163.ꢈꢄm; Yꢇnmꢉi liꢇ
304994337@qq.ꢈꢄm
1
sꢇppꢊꢉmꢉnꢁꢆꢊ ꢃꢆꢁꢆ fꢄꢅ ꢁꢀiꢂ ꢆꢅꢁiꢈꢊꢉ ꢈꢆn bꢉ ꢆꢈꢈꢉꢂꢂꢉꢃ ꢆꢁ ꢀꢁꢁpꢂ://ꢃꢄi.ꢄꢅg/10.1080/14786419.2017.1371159.
2017 Infꢄꢅmꢆ uK limiꢁꢉꢃ, ꢁꢅꢆꢃing ꢆꢂ tꢆyꢊꢄꢅ & Fꢅꢆnꢈiꢂ Gꢅꢄꢇp
©

2
X. DENG ET AL.
1
. Introduction
Chrysin (5,7-dihydroxyflavone) is a natural flavonoid from many plants and has all kinds
of biological activities such as antitumour, antiviral, antibactericidal, anti-inflammatory,
antiallergic, antimutagenic, antianxiolytic and antioxidant effects (Hamilton-Miller 1995; Han
1997; Bae et al. 2000; Lim et al. 2011; Du et al. 2012; Wang et al. 2014; Aksu et al. 2016; Miura
et al. 1995). A lot of studies have been done by synthesis of chrysin derivatives to improve
its pharmaceutical activity. Tran Thanh Dao designed and synthesised 25 chrysin derivatives,
some of which showed great inhibition activities against cyclooxygenase-2 (COX-2) catalysed
prostaglandin E (PGE ) production (Dao et al. 2004), suggesting that antitumour activities
2
2
of chrysin and its derivatives may be related to the COX-2/PGE pathway. Zhu et al. (2014)
2
modified chrysin by adding some hydrophobic groups in the search for potential antitumour
agents.
Salicylic acid (SA) and its derivatives have been used for many years as the leading non-ste-
roidal anti-inflammatory drugs. It was reported that SA and its derivatives prevented tumour
cell growth, induced apoptosis (Grivennikov et al. 2010; Thun et al. 2012) and decreased risk
of gastric carcinoma, colorectal, oesophageal, breast, lung, prostate, liver and skin tumours
(
2
Harris et al. 2005; Kaiser 2012; Sahasrabuddhe et al. 2012; Dovizio et al. 2013; Gamba et al.
013). The antitumour effect of acetylsalicylic acid (ASA) has been owed to its effects on
cyclo-oxygenase (COX) (Loll et al. 1995). Nevertheless, COX negative colon tumour cell line
SW480 went through apoptosis under ASA actions, revealing that ASA also can trigger cell
apoptosis by other mechanisms distinct from COX inhibition (Lai et al. 2008). Recently, it has
been demonstrated that ASA inhibit 6-phosphofructo-1-kinase (PFK) that is one of the key
enzymes in the glycolysis to change tumour glucose utilisation and promote cell apoptosis
(
Spitz et al. 2009).
As antitumour activity is especially important for clinic application, the aim of present
study was to improve the antitumour efficacy of chrysin derivatives. So, in our study, the
-OH of chrysin was modified by adding SA and its derivatives in order to find out some
7
efficient and low toxicity antitumour drugs. A series of chrysin salicylate derivatives were
firstly synthesised and investigated their antitumour activity against three human tumours
and one mice tumour in vitro. Compound 3f (Figure 1) showed the most potent activity
against MGC-803 cells and MFC cells with IC values of 23.83 ± 3.68 and 27.34 ± 5.21 μM,
5
0
respectively. Furthermore, cell cycle assay in vitro, and antitumour efficacy in mice after
administration of compound 3f were also investigated.
Figure 1. sꢁꢅꢇꢈꢁꢇꢅꢉ ꢄf ꢈꢄmpꢄꢇnꢃ 3f.

NATURAL PRODUCT RESEARCH
3
2
. Results and discussion
The synthesis of compounds 2a–f, 3a–f and 4a–f were accomplished according to the gen-
eral pathway illustrated in the Scheme 1. All of the synthetic compounds gave satisfactory
analytical and spectroscopic data, which were in full accordance with their depicted
structures.
The antitumour efficacy of new compounds was evaluated in vitro and in vivo. The antitu-
mour activities in vitro of the chrysin salicylate derivatives 2a–f, 3a–f and 4a–f was researched
on the human tumour cells MCF-7 (michigan tumour foundation-7), HepG2 (human liver
carcinoma cells), MGC-803 (gastric carcinoma cells) and the mice tumour cells MFC (mouse
fore-stomach carcinoma cells) by methyl tetrazolium (MTT) assay. Compounds were tested
over a range of concentrations from 2 to 256 μmol/L, and the calculated IC50 values were
reported in Table 1. Most compounds have good bioactivity to MCF-7 cells, HepG2 cells,
MGC-803cells and MFC cells. Compound 3f was found to show the most potent activity
against MGC-803 cells and MFC cells with IC50 values of 23.83 ± 3.68 and 27.34 ± 5.21 μM,
respectively.
The antitumour growth effect in vivo was evaluated by measuring tumour volume follow-
ing treatment with 5-Fu (1.25 mg/mL, dissolved in saline mixed with 3% Tween 80), different
doses of compound 3f (10, 20, 40 mg/kg, dissolved in saline mixed with 3% Tween 80) and
saline (mixed with 3% Tween 80). As illustrated in Figures 2 and 3, compound 3f inhibited
the tumour growth remarkably by dose-dependent as well compared with the saline and
the result have statistically significant, confirming that compound 3f had antitumour activity.
It was observed that the middle dose and the high dose of compound 3f exhibited stronger
Scheme 1. synꢁꢀꢉꢂiꢂ ꢈꢀꢅyꢂin ꢂꢆꢊiꢈyꢊꢆꢁꢉ ꢃꢉꢅivꢆꢁivꢉꢂ: (ꢆ) Bꢅch ch Bꢅ ꢄꢅ Bꢅch ch ch Bꢅ ꢄꢅ Bꢅch ch ch ch Bꢅ,
2
2
2
2
2
2
2
2
2
K co , ꢆꢈꢉꢁꢄnꢉ; (b)ꢂꢇbꢂꢁiꢁꢇꢁꢉꢃ ꢂꢆꢊiꢈyꢊꢆꢁꢉ, K co , dMF, ꢀꢉꢆꢁing.
2
3
2
3

4
X. DENG ET AL.
Table 1. anꢁi-pꢅꢄꢊifꢉꢅꢆꢁivꢉ ꢆꢈꢁiviꢁy ꢄf ꢈꢄmpꢄꢇnꢃꢂ ꢆgꢆinꢂꢁ ꢁꢀꢉ ꢁꢇmꢄꢇꢅ ꢈꢉꢊꢊ ꢊinꢉꢂ.
IC (μM)
5
0
Compounds
MGC-803
MCF-7
HepG-2
MFC
2
2
2
2
2
2
3
3
3
3
3
3
4
4
4
4
4
4
a
b
c
d
e
f
a
b
c
d
e
f
a
b
c
d
e
f
＞100
＞100
N.d
＞100
＞100
N.d
94.75 ± 4.62
＞100
＞100
N.d
＞100
N.d
89.22 ± 4.37
40.47 ± 2.03
N.d
N.d
N.d
＞100
N.d
N.d
＞100
57.09 ± 3.17
N.d
＞100
＞100
N.d
＞100
＞100
＞100
N.d
＞100
N.d
46.55 ± 2.03
84.14 ± 3.72
＞100
89.18 ± 3.83
79.30 ± 3.62
89.56 ± 3.15
N.d
79.60 ± 4.09
N.d
57.49 ± 3.16
＞100
＞100
＞100
＞100
45.93 ± 3.91
＞100
60.46 ± 3.83
＞100
70.68 ± 4.72
23.83 ± 3.68
82.04 ± 4.54
N.d
74.02 ± 5.22
35.73 ± 4.31
＞100
76.30 ± 4.66
27.34 ± 5.21
＞100
N.d
N.d
N.d
N.d
N.d
91.16 ± 5.37
＞100
67.76 ± 5.46
N.d
N.d
78.83 ± 4.25
67.32 ± 3.47
85.93±5.87
＞100
＞100
＞100
cꢀꢅyꢂin
-Fu
＞100
＞100
5
78.37 ± 1.04
85.59 ± 4.68
Nꢄꢁꢉ: N.d = nꢄꢁ ꢃꢉꢁꢉꢈꢁꢉꢃ.
TIR
9
2.75%
8
6.19%
7
6
4.73%
8.59%
Figure 2. tꢀꢉ tIr vꢆꢊꢇꢉꢂ ꢄf ꢉxꢈiꢂꢉꢃ ꢁꢇmꢄꢇꢅꢂ ꢆꢁ ꢃꢆy 18.tꢀꢉ ꢃiffꢉꢅꢉnꢈꢉꢂ ꢄf ꢁꢀꢉ ꢆvꢉꢅꢆgꢉ ꢄf ꢁꢇmꢄꢇꢅ wꢉigꢀꢁ
ꢆmꢄng ꢁꢀꢉ bꢊꢆnk ꢈꢄnꢁꢅꢄꢊ gꢅꢄꢇp ꢆnꢃ ꢄꢁꢀꢉꢅ gꢅꢄꢇpꢂ wꢉꢅꢉ ꢂꢁꢆꢁiꢂꢁiꢈꢆꢊꢊy ꢂignifiꢈꢆnꢁ (p < 0.05). tꢀꢉ ꢃiffꢉꢅꢉnꢈꢉꢂ
ꢄf ꢁꢀꢉ ꢆvꢉꢅꢆgꢉ ꢄf ꢁꢇmꢄꢇꢅ wꢉigꢀꢁ ꢆmꢄng ꢁꢀꢉ miꢃꢃꢊꢉ ꢃꢄꢂꢉ, ꢁꢀꢉ ꢀigꢀ ꢃꢄꢂꢉ ꢄf ꢈꢄmpꢄꢇnꢃ 3f ꢆnꢃ 5-Fꢇ gꢅꢄꢇpꢂ
wꢉꢅꢉ ꢂꢁꢆꢁiꢂꢁiꢈꢆꢊꢊy ꢂignifiꢈꢆnꢁ (p < 0.05).
tumour regression, with TIR of 86.19 and 92.75%, compared with the 5-Fu injection (TIR of
68.59%). The differences of the average of tumour weight among the middle dose, the high
dose of compound 3f and 5-Fu groups were statistically significant (p < 0.05). The results
confirmed that the antitumour efficacy of compound 3f is superior to 5-Fu. Figure 4 illustrated
the growth in body weight during the 18-day experimental period. The gradual increase in
body weight among the low and middle dose of compound 3f groups was consistent with
that of the saline group, which represented the natural growth in body weight of MFC
tumour-bearing mice. Moreover, the fur of the mice is normal by treating with different doses
of compound 3f, but the mice treated with 5-Fu have obvious change on hair removal and

NATURAL PRODUCT RESEARCH
5
Figure 3. tꢇmꢄꢇꢅ vꢄꢊꢇmꢉ gꢅꢄwꢁꢀ ꢈꢇꢅvꢉꢂ ꢄf ꢁꢀꢉ miꢈꢉ ꢆfꢁꢉꢅ ꢁꢅꢉꢆꢁmꢉnꢁ wiꢁꢀ 5-Fꢇ (1.25 mg/ml, ꢃiꢂꢂꢄꢊvꢉꢃ in
ꢂꢆꢊinꢉ mixꢉꢃ wiꢁꢀ 3% twꢉꢉn 80), ꢃiffꢉꢅꢉnꢁ ꢃꢄꢂꢉꢂ ꢄf ꢈꢄmpꢄꢇnꢃ 3f (10, 20, 40 mg/kg, ꢃiꢂꢂꢄꢊvꢉꢃ in ꢂꢆꢊinꢉ
mixꢉꢃ wiꢁꢀ 3% twꢉꢉn 80) ꢆnꢃ ꢂꢆꢊinꢉ (mixꢉꢃ wiꢁꢀ 3%twꢉꢉn 80). dꢆꢁꢆ wꢉꢅꢉ ꢂꢀꢄwꢉꢃ ꢆꢂ ꢆ mꢉꢆn ± sd (n = 6
ꢆnꢃ ꢁꢀꢉ miꢈꢉ nꢇmbꢉꢅ ꢄf bꢊꢆnk ꢈꢄnꢁꢅꢄꢊ iꢂ 9).
Figure 4. Bꢄꢃy wꢉigꢀꢁ ꢉvꢄꢊꢇꢁiꢄn ꢈꢇꢅvꢉꢂ ꢄf ꢁꢀꢉ miꢈꢉ ꢆfꢁꢉꢅ ꢁꢅꢉꢆꢁmꢉnꢁ wiꢁꢀ 5-Fꢇ (1.25 mg/ml, ꢃiꢂꢂꢄꢊvꢉꢃ in
ꢂꢆꢊinꢉ mixꢉꢃ wiꢁꢀ 3% twꢉꢉn 80), ꢃiffꢉꢅꢉnꢁ ꢃꢄꢂꢉꢂ ꢄf ꢈꢄmpꢄꢇnꢃ 3f (10, 20, 40 mg/kg, ꢃiꢂꢂꢄꢊvꢉꢃ in ꢂꢆꢊinꢉ
mixꢉꢃ wiꢁꢀ 3% twꢉꢉn 80) ꢆnꢃ ꢂꢆꢊinꢉ (mixꢉꢃ wiꢁꢀ 3%twꢉꢉn 80). dꢆꢁꢆ wꢉꢅꢉ ꢂꢀꢄwꢉꢃ ꢆꢂ ꢆ mꢉꢆn ± sd (n = 6
ꢆnꢃ ꢁꢀꢉ miꢈꢉ nꢇmbꢉꢅ ꢄf bꢊꢆnk ꢈꢄnꢁꢅꢄꢊ iꢂ 9).
body weight, demonstrating that the toxicity of compound 3f was lower than that of positive
control 5-Fu.
MFC cells were treated with compound 3f at 0, 10, 20, 40 μM for 24 h to detect cell cycle
distribution. As indicated in Figure 5, with the increase of drug concentration, the percentage
of cells in G1 phase increased, the percentage of cells in S phase decreased and G2/M change
is not obvious. It can be shown that tumour cells occurred G1/S block under the inhibiting
effect of compound 3f.

6
X. DENG ET AL.
Figure 5. Fꢊꢄw ꢈyꢁꢄmꢉꢁꢅy ꢆnꢆꢊyꢂiꢂ ꢄf ꢈꢉꢊꢊ ꢈyꢈꢊꢉ ꢃiꢂꢁꢅibꢇꢁiꢄn fꢄꢅ MFc ꢈꢉꢊꢊꢂ ꢁꢅꢉꢆꢁꢉꢃ wiꢁꢀ ꢈꢄmpꢄꢇnꢃ 3f (0,
0, 20, 40 μmꢄꢊ/l) fꢄꢅ 24 ꢀ.
1
3
. Experimental
3
.1. Synthesis
All chemicals (reagent grade) used were commercially available. Chrysin (>98%) was pur-
1
chased from Aladdin-Reagent Co., Ltd (China). H NMR were recorded on a Bruker AVANCE
instrument (400 MHz). Melting points (uncorrected) were determined on an XT4 MP appa-
ratus (Taike Corp., Beijing, China). ESI-MS spectra were recorded on a Mariner System 5304
Mass spectrometer.
3
.2. General method for synthesis of compounds 1a–1c
To a stirring solution of chrysin (compound 1) in acetone, K CO was added and then
2
3
1,2-dibromoethane or 1,3-dibromopropane or 1,4-dibromobutane was added dropwise to
give compound 1a–1c.
3
.3. General method for synthesis of compounds 2a–2f
To a solution of 1a (0.36 g, 1 mmol) in 10 mL of anhydrous DMF was added Methyl salicylate
0.76 g, 5 mmol), K CO (0.12 g, 1 mmol), followed by heating at 60 °C for 6 h. To the reaction
(
2
3
mixture was added ice water, dropwise. The mixture was filtered, washed with water, dried
over Na SO and concentrated. The residue was purified with a silica gel column and was
2
4
eluted with EA/PE 1:8 to afford 2a (0.20 g, 46%).
Compounds 2b–4f were prepared in analogy.
1
The H NMR and ESI-MS spectra data of compounds 2a–4f were supplied as supplemen-
tary material.

NATURAL PRODUCT RESEARCH
7
3
.4. In vitro antitumour efficacy
The human tumour cells MCF-7, HepG2, MGC-803 and the mice tumour cells MFC were
purchased from the Type Culture Collection of the Chinese Academy of Sciences, Shanghai,
China. Cells cultured in Dulbecco’s Modified Eagle’s Medium (DMEM, Gibco, NY, USA) con-
taining 10% foetal bovine serum at 37 °C in a humidified incubator with 5% CO . MCF-7,
2
HepG2, MGC-803 and MFC cells were chosen to evaluate the antitumour activity in vitro.
3
Cells were plated in 96-well microtitre plates at a density of 8 × 10 /well and incubated in a
humidified atmosphere with 5% CO at 37 °C for 48 h. Test compounds were added onto
2
triplicate wells with different concentrations and 0.1% DMSO for control. After they had been
incubated for 48 h, 20μL of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bro-
mide) solution (5 mg/mL) was added to each well and the plate was incubated for an addi-
tional 4 h. The formazan was dissolved in 100 μL of DMSO. The absorbance (OD) was read
on a WellscanMK-2 microplate reader (Labsystems) at 570 nm. The concentration causing
5
0% inhibition of cell growth (IC ) was determined by the Logit method. All experiments
50
were performed three times.
3
.5. In vivo antitumour efficacy
All experiments with animals were performed in compliance with the relevant laws and
institutional guidelines of China Institute of Science and Technology and institutional com-
mittees have approved the experiments. Kunming male mice (University of South China,
China) were used for in vivo experiments. Gastric carcinoma was chosen as a model tumour
to research the antitumour efficacy of the compound 3f. Gastric tumour-bearing mice were
established by subcutaneous injection of MFC cells in the ventral part that suspended in
7
saline to 1 × 10 /0.2 mL/mouse (defined as day 0). On day 1, the mice were randomly divided
into five groups (n = 6 and the mice number of blank control is 9). The mice were treated
with 5-Fu (1.25 mg/mL, dissolved in saline mixed with 3%Tween 80), different doses of com-
pound 3f (10, 20, 40 mg/kg, dissolved in saline mixed with 3% Tween 80) and saline (mixed
with 3% Tween 80) (blank control) via intraperitoneal injection on days 2, 5, 8, 11 and 14.
On day 6, tumour volumes were monitored every other day by measuring two perpen-
dicular diameters using Vernier caliper and calculated using the formula: Volume =
2
0
.5 × Length×(Width) . Body weights were recorded every other day. On day 18, the animals
were sacrificed and the tumour mass was dissected, weighed and photographed. The tumour
inhibition ratio (TIR) was calculated using the formula: TIR (%) = (1−Wt/Ws) × 100%, where
Wt and Ws represent the average tumour weight of the treatment and saline groups,
respectively.
3
.6. In vitro cell cycle assay
The MFC cells were incubated with different concentrations of compound 3f (0, 10,
0,40 μmol/L) in a six-well plate. After 24 h coculture, the cells were washed twice with cold
2
PBS and then resuspended cells with cold PBS. MFC cells were fixed with stored in 70% cold
ethanol for 12 h at 4 °C. Then add 500 μl of Propidium staining to each tube. The cells were
gently vortex and incubated for 30 min at RT (37 °C) in the dark. The cells were analysed by
flow cytometry within 24 h.

8
X. DENG ET AL.
4
. Conclusion
In conclusion, a series of chrysin salicylate derivatives that some of them with good bioac-
tivity have been designed and synthesised successfully. These compounds were exhibited
moderate to good antitumour activity against MCF-7 cells, HepG2 cells, MGC-803cells and
MFC cells. Furthermore, compound 3f showed the most potent activity against MGC-803
cells and MFC cells with IC50 values of 23.83 ± 3.68 and 27.34 ± 5.21 μM, respectively. The
flow cytometry assay reconfirmed that compound 3f inhibited tumour cells by making
tumour cells occurred G1/S block. Moreover, it was evident that compound 3f had good
antitumour activity and low toxicity in vivo. The mechanism of action of these chrysin salic-
ylate derivatives with good bioactivity is unknown, but COX-2 and PFK have been suggested
by us as a possible factor. The next work will focus on investigating the mechanism of action
of these chrysin salicylate derivatives. In a word, these derivatives can be recommended as
new medicine to develop new antitumour agents.
Acknowledgement
The author thanks the Department of Laboratory Animal Science for the support of animals experiments.
Disclosure statement
The authors declare that there are no conflicts of interest.
Funding
This work was supported in part by the Construct Program of the key Discipline in Hunan Province and
Hunan Province Cooperative Innovation Center for Molecular Target New Drug study.
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