Design, synthesis, and anti-tumor activities of novel triphenylethylene- coumarin hybrids, and their interactions with Ct-DNA

Article abstract of DOI:10.1016/j.bmcl.2013.07.009

Novel triphenylethylene-coumarin hybrid derivatives containing different amounts of amino side chains were designed and synthesized in good yields under microwave radiation. The derivatives 5b-d which possessed two amino side chains (except morpholinyl) showed a broad-spectrum and good anti-proliferative activity against five tumor cells and low cytotoxicity in osteoblast. UV-vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation exhibited that compounds 10c, 5c, and 13c bearing amino side chain (except morpholinyl) on 4-phenyl had significant interactions with Ct-DNA by the intercalative mode of binding. Structure-activity relationships (SARs) analysis suggested that the amino alkyl chain would play an important role both in the compounds against tumor cells proliferation and their interactions with DNA.

Full text of DOI:10.1016/j.bmcl.2013.07.009

Accepted Manuscript
Design, synthesis, and anti-tumor activities of novel triphenylethylene-coumar‐
in hybrids, and their interactions with Ct-DNA
Hua Chen, Shuai Li, Yuchao Yao, Likai Zhou, Jianpeng Zhao, Yunjing Gu,
Kerang Wang, Xiaoliu Li
PII:
S0960-894X(13)00843-3
DOI:
http://dx.doi.org/10.1016/j.bmcl.2013.07.009
BMCL 20674
Reference:
To appear in:
Bioorganic & Medicinal Chemistry Letters
Received Date:
Revised Date:
Accepted Date:
23 April 2013
28 June 2013
2 July 2013
Please cite this article as: Chen, H., Li, S., Yao, Y., Zhou, L., Zhao, J., Gu, Y., Wang, K., Li, X., Design, synthesis,
and anti-tumor activities of novel triphenylethylene-coumarin hybrids, and their interactions with Ct-DNA,
Bioorganic & Medicinal Chemistry Letters (2013), doi: http://dx.doi.org/10.1016/j.bmcl.2013.07.009
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Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com
Design, synthesis, and anti-tumor activities of novel triphenylethylene-coumarin
hybrids, and their interactions with Ct-DNA
Hua Chen,* Shuai Li, Yuchao Yao, Likai Zhou, Jianpeng Zhao, Yunjing Gu, Kerang Wang, Xiaoliu Li*
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Revised
Accepted
Available online
Novel triphenylethylene-coumarin hybrid derivatives containing different amounts of amino side
chains were designed and synthesized in good yields under microwave radiation. The derivatives
5b-d which possessed two amino side chains (except morpholinyl) showed a broad-spectrum
and good anti-proliferative activity against five tumor cells and low cytotoxicity in osteoblast.
UV-Vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation
exhibited that compounds 10c, 5c, and 13c bearing amino side chain (except morpholinyl) on 4-
phenyl had significant interactions with Ct-DNA by the intercalative mode of binding. Structure
activity relationships (SARs) analysis suggested that the amino alkyl chain would play an
important role both in the compounds against tumor cells proliferation and their interactions
with DNA.
Keywords:
Coumarin
Triphenylethylene
Anti-tumor activities
DNA binding property
2013 Elsevier Ltd. All rights reserved.
Cancer is at present one of the most leading causes of death in
the world. Many novel chemotherapeutic agents derived from
natural products have been well developed for cancer treatment.1
Coumarins are a wide group of naturally occurring compounds
and represent a significant source of inspiration for the new anti-
cancer agents.2 They have a variety of biological activities such
as anti-cancer, anti-HIV, antimicrobial, and anti-inflammatory.3
As the anti-tumor agents, they can act on the cancer formation by
interfering the cellular proliferation.3a,3b,4 Due to their potential
applications in cancer therapy, extensive studies have been
carried out on the design and synthesis of coumarin derivatives
with improved anticancer activity.5 Based on the combination
principle of drug design,6 coupling coumarin with different
bioactive molecules is one of the effective ways. Adopting this
approach, stilbene-, chalcone- and pyrazole-commarin hybrid
compounds2,5a,5c have exhibited significant anti-tumor activities.
On the other hand, triphenylethylene derivatives such as
tamoxifen have been successfully used in the treatment of breast
cancer.7 However, the triphenylethylene-coumarin hybrids in
which the 3,4-double bond of the coumarin nucleus fix the
disposition of the double bond of ethylene are less explored for
the anti-tumor drug discovery. To the best of our knowledge,
there was only one report of such 3,4-diphenyl coumarin
derivatives8 which were studied as the new selective estrogen
receptor modulator (SERMs).9 The promising anti-cancer
activities of coumarin and triphenylethylene prompted us to
explore their structural hybrids for the development of new anti-
tumor drug. Herein, we would like to report the design and
synthesis of the novel triphenylethylene-coumarin hybrid
derivatives containing different amounts of amino side chains
which were generally introduced to the fused heterocycles to
improve their solubility and biological activity.10 The anti-
proliferative activity against tumor cells and the cytotoxicity
towards normal cell (osteoblast) of the new compounds were
preliminary evaluated. Since many coumarins as DNA binders
exhibited their antitumor efficacy by inhibiting DNA
replication,11 in order to seek for the potential anti-tumor target
of our coumarin derivatives, the interactions of the compounds
with Ct-DNA were also tested by UV-Vis, fluorescence, and
circular dichroism (CD) spectroscopies and thermal denaturation
experiment.
OAc
OH
O
(b)
(a)
+
HO
OH
OH
HO
OH
AcO
O
O
COOH
1
2
R
Br
O
O
OH
(e)
(c)
(d)
Br
R
O
O
O
O
O
O
HO
O
O
5a-d
3
4
(f)
OH
OH
(e)
R
Br
O
O
O
O
O
O
7a-d
6
N
O
N
N
R=
N
a
b
c
d
———
*Correspondence: E-mail: lixl@hbu.cn and hua-todd@163.com; Tel & Fax.: 0086-312-5971116.

Scheme 1 Synthesis of compounds 5a-d and 7a-d. Reagents and conditions:
(a) POCl3, ZnCl2, sulfolane, 65 oC, 2 h, 66%; (b) phenyl acetic acid, Ac2O,
Et3N, M.W., 130 oC, 30 min, 82%. (c) 3N HCl, acetone, reflux, 99%; (d)
BrCH2CH2Br (20.0 equiv.), dry acetone, K2CO3 (6.0 equiv.), M.W., 130 oC,
30 min, 73%; (e) RH, THF, M.W., 120 oC, 30 min, 80% - 91%; (f)
BrCH2CH2Br (8.0 equiv.), dry acetone, K2CO3 (2.0 equiv.), M.W., 130 oC, 30
min, 49%.
on the side chain, for example the morpholinyl, demonstrated a
detrimental effect on anti-proliferative activity. It seemed that
compounds 5b-d exhibited a broad-spectrum anti-proliferative
activity.
Table 1. Anti-proliferative activity of compounds against the cancer cell lines
IC50 (µM)
Compds
A549
>100 a
K562
>100
MCF-7
>100
Bel-7402
N. T.b
HL-60
N. T.
3
8
>100
>100
>100
N. T.
N. T.
>100
>100
>100
N. T.
N. T.
11
5a
>100
>100
>100
>100
>100
6.31 ± 0.42
6.64 ± 0.44
8.31 ± 0.42
94.10 ± 4.06
54.28 ± 3.17
91.25 ± 5.12
>100
4.58 ± 1.31
2.91 ± 0.09
3.79 ± 0.29
>100
12.35 ± 1.60
11.36 ± 1.60
7.90 ± 0.82
>100
8.66 ± 0.61
8.19 ± 0.52
8.04 ± 0.30
N. T.
5.93 ± 0.19
5.28 ± 5.23
3.98 ± 0.12
N. T.
5b
5c
5d
7a
44.54 ± 3.54
81.25 ± 5.12
>100
50.00 ± 3.48
86.57 ± 4.64
>100
N. T.
N. T.
7b
N. T.
N. T.
7c
N. T.
N. T.
7d
Scheme 2 Synthesis of compounds 10a-d and 13a-d.
>100
>100
>100
N. T.
N. T.
10a
10b
10c
10d
13a
13b
13c
13d
Tamoxifen
Cisplatin
89.84 ± 7.31
23.43 ± 1.42
60.78 ± 4.58
>100
93.26 ± 8.38
19.64 ± 1.37
88.79 ± 5.38
>100
>100
N. T.
N. T.
Synthesis of the 3,4-diphenyl coumarins (5a-d and 7a-d) was
achieved according to the previous procedures8 as outlined in
Scheme 1. Briefly, commercially available resorcinol reacted
with 4-hydroxybenzoic acid to yield the benzophenone (1) under
Fries reaction conditions. The treatment of 1 with phenyl acetic
acid mainly gave the acylated 3,4-diaryl coumarin derivative (2)
via Perkin reaction route. The acetyl groups in 2 were removed in
acidic solution to obtain 3 and further coupled with different
amounts of 1,2-dibromoethane to obtain 4 or 6. The SN2
nucleophilic substitution of 4 or 6 with a variety of basic amine
provided the final products 5a-d containing two amino alkyl
chains or 7a-d (poor solubility) containing one side chain on 7-
position, respectively. Microwave radiation (M.W.) could
efficiently improve the Perkin reaction and the nucleophilic
substitution. Following the same procedures, the target products
13a-d containing three amino side chains and 10a-d containing
one amino side chain at 4-phenyl were synthesized from the
starting materials, 3-methoxyphenol and 4-hydroxyphenylacetic
acid, respectively (Scheme 2).
29.64 ± 1.84
76.66 ± 5.67
>100
N. T.
N. T.
N. T.
N. T.
N. T.
N. T.
86.29 ± 6.39
56.27 ± 4.05
45.16 ± 3.28
N. T.
75.33 ± 6.24
39.44 ± 4.62
41.88 ± 4.35
N. T.
92.81 ± 8.06
48.20 ± 5.61
68.78 ± 5.16
13.45 ± 1.92
16.22 ± 3.35
N. T.
N. T.
N. T.
N. T.
N. T.
N. T.
N. T.
N. T.
20.40 ± 5.67
12.92 ± 1.36
14.12 ± 1.68
13.36 ± 1.47
[a] No activity; [b] Not Test.
The active compounds 5b-d were also evaluated for possible
cytotoxicity in normal cell, for example, osteoblast (Table 2). It
could be found that all the tested compounds did not significantly
affect the growth of osteoblasts, suggesting that these molecules
had selectivity for inducing growth inhibition of tumor cells. The
results suggested that compounds 5b-d might be suitable as
potential drug candidate for cancer chemotherapy.
Table 2. Cytotoxicity of compounds 5b-d towards osteoblast.a
The structures of all the newly compounds were determined
by NMR, MS, and elemental analysis. Both analytical and
spectral data of compounds are in agreement with the proposed
structures. The amino side chain was on the 7-position in 7 was
confirmed by the absence of the 7-OH proton signal in d6-DMSO
1H NMR in comparison to that in 3.
Compd
% cell cytotoxicity
s
1 µM
10 µM
-6.7 ± 1.2**
-2.6 ± 1.4
3.2 ± 1.5*
20 µM
40 µM
100 µM
-5.1 ± 2.3b
-8.0 ± 1.9*c
-3.1 ± 2.2
10.1 ± 1.6*
7.4 ± 1.1
18.2 ± 0.9**
14.2 ± 1.2*
20.6 ± 0. 7*
36.1 ± 0.8***
39.2 ± 0.9***
42.2 ± 0.2***
5b
5c
5d
12.2 ± 0.9**
[a] Primary cultured osteoblasts (separated from newborn mice skull) were
treated with active coumarin compounds at varying concentrations for 48 h
and induced cell death was measured with MTT assay; [b] The data presented
are means ± SEM and six repilcates were performed. *p < 0.05, **p < 0.01,
***p < 0.001 with respect to the untreated cells.
Compounds 5a-d, 7a-d, 10a-d, and 13a-d and their precursors
3, 8, and 11 were subjected to anti-proliferative tests against the
following cancer cell lines, A549 (human lung cancer), K562
(chronic myeloid leukemia), MCF-7 (human breast cancer), Bel-
7402 (human hepatocellular carcinoma), and HL-60 (human
promyelocytic leukemia) cells. Cisplatin and tamoxifen were
used as positive controls. As shown in table 1, three compounds
5b-d containing two amino alkyl chains (5b R = pyrrolidinyl, 5c
R = piperidinyl, 5d R = NEt2) exhibited significant anti-
proliferative activity against five cancer cells at IC50 of near 10
µM, and better than the positive controls. Four compounds 7b,
10c, 13c, and 13d showed moderate anti-tumor activities and the
others left showed weak or no activity. Neither the compounds
with morpholinyl alky chain nor the precursors without the
amino side chain (3, 8, and 11) expressed anti-proliferative
activity. These observations suggested that: 1) the number of the
amino alkyl chain on the 3,4-diphenyl coumarin had notable
impact on anti-proliferative activity, and two side chains were
more preferable for this activity; 2) the weaker basic amino group
In order to seek for the potential anti-tumor target of our
coumarin derivatives, UV-Vis, fluorescence, and CD
spectroscopies and DNA thermal denaturation experiment were
used to ascertain the DNA binding properties of compounds 3,
10c, 5a, 5c, and 13c with calf thymus (Ct) DNA.
The DNA binding properties of compounds 3, 10c, 5a, 5c, and
13c with Ct-DNA were investigated by UV-Vis spectra in
phosphate buffer (10 mM, pH 7.4) containing 50 mM NaCl at 25
oC. As shown in Figure 1, the absorption intensities of
compounds 3, 10c, and 5a enhanced with increased Ct-DNA
concentrations in low hyperchromities of 8%, 12% and 13%,
respectively, while the intensities of compounds 5c and 13c
decreased in middle hypochromicities of 23% and 25%,

respectively. These results indicated that the binding capacities of
the 3,4-diphenyl coumarin derivatives and Ct-DNA would be
enhanced as the increasing amounts of amino side chains (except
morpholinyl). The maximum absorption (λmax) of all the tested
coumarin derivatives showed rarely bathochromic shift in the
presence of increasing concentration of Ct-DNA, except that the
λmax of compound 13c exhibited obviously red shift (9 nm). The
observed spectral changes (significant red shift and
hypochromism) in compound 13c implied that 13c would insert
into the base pairs of DNA as a DNA-intercalating agent,12 while
10c (middle hypochromism), 5a, and 5c (low hyperchromism but
little shift) possibly acted in a same binding mode with DNA.13
There was no interaction between 3 and Ct-DNA.
function of Ct-DNA concentrations, where F0 and F are the
fluorescence intensity without and with Ct-DNA, respectively.
Stern-Volmer analysis gave deep insight into the binding
efficiency of fluorescence enhancement of the coumarins with
increasing concentrations of Ct-DNA14a. The calculated binding
efficiency were 5.41 × 102 M-1, 3.12 × 103 M-1, 2.68 × 102 M-1,
4.21 × 103 M-1 and 3.16 × 104 M-1 of compounds 3, 10c, 5a, 5c,
and 13c (Fig. 3, inset), respectively.16 The Stern-Volmer plots
indicate that the fluorescence of compound 13c possessing three
amino side chains is highly sensitive to the Ct-DNA
concentrations.
1.10
1.6
1.0k
1.08
1.5
1.06
1.4
1.2k
1.04
1.02
1.3
1.2
1.1
800.0
600.0
400.0
200.0
0.0
6.0x10-51.2x10-41.8x10-4
0.0
0.18
0.15
0.12
0.09
0.06
0.03
0.00
6.0x10-5 1.2x10-4 1.8x10-4
0.15
0.12
0.09
0.06
0.03
0.00
0.0
0.123
0.120
0.117
0.114
0.111
800.0
400.0
0.0
Concentration of Ct-DNA
0.165
0.162
0.159
0.156
0.153
Concentration of Ct-DNA
5.0x10-51.0x10-41.5x10-4
0.0
Concentration of Ct-DNA
5.0x10-51.0x10-41.5x10-4
0.0
Concentration of Ct-DNA
400 450 500 550 600
Wavelength/nm
400
500
600
Wavelength/nm
3
10c
350
400
450
500
320 340 360 380 400 420 440
Wavelength/nm
Wavelength/nm
1.8
1.6
1.4
1.2
1.07
1.06
1.05
1.04
1.5k
1.0k
500.0
0.0
600
3
10c
1.03
0.0
0.18
0.17
0.16
0.15
0.14
6.0x10-5 1.2x10-4 1.8x10-4
6.0x10-5 1.2x10-4 1.8x10-4
0.0
0.165
0.160
0.155
0.18
Concentration of Ct-DNA
0.18
0.15
0.12
0.09
0.06
0.03
0.00
400
200
0
Concentration of Ct-DNA
0.15
0.12
0.09
0.06
0.03
0.00
0.150
0.0
5.0x10-51.0x10-41.5x10-4
0.0
5.0x10-5 1.0x10-4 1.5x10-4
Concentration of Ct-DNA
Concentration of Ct-DNA
400
500
600
400
500
600
Wavelength/nm
Wavelength/nm
5a
5c
300 330 360 390 420 450
Wavelength/nm
300 320 340 360 380 400 420
Wavelength/nm
4k
6
5
4
3
2
3k
2k
1k
0
5a
5c
0.15
0.14
0.13
0.12
0.11
1
6.0x10-5 1.2x10-4 1.8x10-4
0.0
0.15
0.12
0.09
0.06
0.03
0.00
Concentration of Ct-DNA
5.0x10-51.0x10-41.5x10-4
Concentration of Ct-DNA
0.0
400
500
600
Wavelength/nm
300 320 340 360 380 400 420 440
Wavelength/nm
13c
Fig. 2 Fluorescence spectral changes of 3 (λex= 336 nm), 10c (λex= 331 nm),
5a (λex= 332 nm), 5c (λex= 331 nm), and 13c (λex= 329 nm) at the
concentration of 5.0×10-6 M upon addition of Ct-DNA (0 µΜ- 90 µΜ) in
phosphate buffer (10 mΜ, pH 7.4) containing 50 mM NaCl and 4% DMSO at
25 oC. Both excitation and emission slit widths were 10.0 nm. Inset: Stern-
Volmer plots for the observed fluorescence enhancement upon addition of Ct-
DNA to the coumarin derivatives.
13c
Fig. 1 UV-Vis spectral changes of compounds 3, 10c, 5a, 5c, and 13c at the
concentration of 1.0×10-5 M upon addition of Ct-DNA (0 µM-180 µΜ) in
phosphate buffer (10 mΜ, pH 7.4) containing 50 mM NaCl and 4% DMSO at
25 oC. Inset: the fitting plots for 3, 10c, 5a, 5c, and 13c with Ct-DNA
obtained at the maximum absorption.
The fluorescence properties were performed to investigate the
interactions between compounds 3, 10c, 5a, 5c, and 13c and Ct-
DNA in phosphate buffer (10 mM, pH 7.4) containing 50 mM
CD is a useful technique to investigate the conformational
changes in DNA morphology during small molecules-DNA
interactions. As shown in Figure 3, the CD spectrum of free Ct-
o
NaCl at 25 C. As shown in Figure 2, compounds 10c, 5c, and
DNA showed
a negative band at 247 nm due to the
13c which had amino side chain on 4-phenyl showed similar
binding properties with Ct-DNA around 455 nm in the
fluorescence spectra. Upon addition of DNA, fluorescence
intensities increased markedly, possibly due to the coplanar
modulation of the conformation of 3- and 4-phenyl groups
induced by Ct-DNA.14 The maximum emission bands of 10c and
5c didn’t shift, while the band of 13c was blue shifted ~ 17 nm.
These observations implied that 10c, 5c, and 13c entered Ct-
DNA-stacking region with lower polarity than the buffer
solution,15 and intercalated into the bases of the Ct-DNA.14a The
fluorescence intensities of 3 and 5a with morpholinyl alky chain
increased slightly with increased Ct-DNA concentrations, which
was consistent with their low hyperchromities on UV. These
results demonstrated that there were nearly no interactions
between the compound 3 or 5a and Ct-DNA. The observed
fluorescence intensities were quantified by plotting F/F0 as a
polynucleotide helicity, and a positive band at 277 nm due to the
base staking, which indicated that the Ct-DNA existed in the
right-band B form.17 Upon addition of compound 13c, the
intensity of the positive band at 277 nm increased obviously,
while the intensity of the negative band at 247 nm decreased
(without significant wavelength change). This observation
implied that 13c could intercalate DNA and induce a B to A
conformational change on Ct-DNA.18 For compounds 10c, 5a,
and 5c, the positive intensity changes found at 277 nm suggested
that these compounds could insert into the bases of the Ct-DNA
with the order of the intensity change of 5c (middle intercalation)
> 10c ≈ 5a (poor intercalation), which was in agreement with the
UV-Vis analysis. The little intensity change of 3 with Ct-DNA
further demonstrated that there was no interaction between them.
Additional, weak positive induced circular dichroisms (ICD)
signals were observed in the region of the characteristic

absorption of these triphenylethylene-coumarin hybrid
derivatives (350-500 nm), which indicated that 10c, 5a, 5c, and
intercalative mode of binding properties with DNA, such as 10c,
5c, and 13c. As the amount of amino side chains (except
morpholinyl) increases, the intercalative binding is more efficient,
possibly due to the extra noncovalent force between the chains
and DNA grooves.21 Among them, compound 13c containing
three amino side chains possessed potential application as novel
DNA staining agent. In addition, 5c (R = piperidinyl) endowed
with good anti-tumor activities showed significant binding force
with DNA. In contrast, 3 (without amino side chain) and 5a (R =
morpholinyl) showed no or very low interactions with DNA and
no anti-tumor activities. These observations allowed us to
postulate that DNA might be one of the potential targets for such
triphenylethylene-coumarin hybrids as anti-tumor drug
candidates.
13c intercalated DNA with
a
vertical orientation in the
intercalation pocket.19
8
Ct-DNA
Ct-DNA+3
Ct-DNA+10c
Ct-DNA+5a
Ct-DNA+5c
Ct-DNA+13c
4
0
0.8
0.4
0.0
-4
-8
-0.4
-0.8
350
400
450
500
Wavelength/nm
240
280
320
360
Wavelength/nm
Fig. 3 CD spectra of Ct-DNA (5.0×10-5 M) in the absence and presence of 3,
10c, 5a, 5c, and 13c (2.0×10-5 M) in phosphate buffer (10 mM, pH 7.4)
containing 50 mM NaCl and 4% DMSO at 25 oC.
In summary, a series of novel triphenylethylene-coumarin
hybrid
derivatives
(triphenylethylene-coumarin
hybrids)
possessing different amounts of amino side chains were designed
and synthesized based on the triphenylethylene template.
Compounds 5b-d containing two amino (except morpholinyl)
side chains showed a broad-spectrum and excellent anti-tumor
activity and low cytotoxicity in osteoblast, which suggested that
they might be suitable as potential drug candidate for cancer
chemotherapy. The SARs suggested that the amount of the amino
alkyl chain on the 3,4-diphenyl coumarin had profound effects on
their anti-proliferative activities and DNA binding properties.
The similar trends implied that DNA might be one of the
potential targets for such 3,4-diphenyl coumarins as anti-cancer
drugs.
It is well known that the temperature at which a half of a DNA
sample melts is known as the melting temperature (Tm). A change
of Tm may be observed if a molecule binds with DNA.20 Thus the
thermal behavior of DNA in the presence of the
triphenylethylene-coumarin hybrid derivatives provides useful
information on the conformational changes and the strength of
the DNA-compound complexes. The melting curves of Ct-DNA
in the absence and presence of 3, 10c, 5a, 5c, and 13c are
illustrated in Figure 4 and Table 3, respectively. The Tm value for
the free Ct-DNA was 67.5 oC. Upon addition of 10c, 5c, and 13c,
obvious changes in the DNA melting temperature were observed.
o
The Tm values increased to 70.7, 71.8 and 77.6 C, respectively,
and the levels of the increased melting temperature (∆Tm)
induced by DNA-compound interactions were 3.2, 4.3 and 8.8
oC, respectively. Compounds 3 and 5a possessed lower DNA
melting temperature than other compounds, and the ∆Tm values
Acknowledgments
This work was supported by the 973 Program
(2010CB534913) and the National Natural Science Foundation
of China (NSFC) (20902016).
o
were 1.1 and 2.0 C, respectively. These results illuminated that
compounds 10c, 5c, and 13c with various amounts of amino side
chain (except morpholinyl) on 4-phenyl exhibited middle
affinities with Ct-DNA, consistent with the results from the
fluorescence data.
Supplementary data
Experimental procedures and characterization data for
compounds 5a-d, 7a-d, 10a-d, and 13a-d are available.
Supplementary data associated with this article can be found, in
the online version, at doi:
1.0
Ct-DNA
Ct-DNA+3
Ct-DNA+5a
Ct-DNA+10c
Ct-DNA+5c
0.8
Ct-DNA+13c
0.6
References and notes
0.4
0.2
1. Cragg, G. M.; Grothaus, P. G.; Newman, D. J. Chem. Rev. 2009, 109,
3012.
0.0
2. Belluti, F.; Fontana, G.; Dal Bo, L.; Carenini, N.; Giommarelli, C.;
Zunino, F. Bioorg. Med. Chem. 2010, 18, 3543.
55 60 65 70 75 80 85
o
Temperature( C)
Fig. 4 DNA melting curves for Ct-DNA (5.0×10-5 M) in the absence and
presence of 3, 10c, 5a, 5c, and 13c with concentration of 5.0×10-6 M in
phosphate buffer (1 mM, pH 7.4) containing 5 mM NaCl and 4% DMSO at
25oC.
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Table 3. Average Tm and ∆Tm for Ct-DNA in the absence and presence of 3,
10c, 5a, 5c, and 13c
Compds
Ct-DNA
3
Tm (oC)
67.5
68.6
70.7
69.5
71.8
77.6
∆Tm (oC)
0
1.1
3.2
10c
2.0
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Graphical Abstract
Leave this area blank for abstract info.
Design, synthesis, and anti-tumor
activities of novel triphenylethylene-
coumarin hybrids, and their interactions
with Ct-DNA
Hua Chen, Shuai Li, Yuchao Yao, Likai Zhou, Jianpeng Zhao, Yunjing Gu, Kerang Wang, Xiaoliu Li