Strong in vitro and in vivo cytotoxic effects of two platinum(II) complexes with cryptolepine derivatives

Article abstract of DOI:10.1007/s00044-021-02739-0

Two mononuclear Pt(II) compounds, [Pt(BQL1)Cl]Cl (BQL1-Pt) and [Pt(BQL2)Cl]Cl (BQL2-Pt), with [5-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-pentyl]-bis-pyridin-2-ylmethyl-amine (BQL1) and [9-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-nonyl]-bis-pyridin-2-ylmethyl-amine (BQL2), were prepared as new chemotypes for potential antitumor agents. In this study, the effects of cryptolepine derivatives in BQL1-Pt, 2,2′-dipicolylamine Pt(II) complex, and BQL2-Pt on cellular Pt(II) accumulation, cytotoxicity, and in vitro and in vivo antitumor activities against T-24 cancer cells and normal HL-7702 cells were evaluated. BQL1-Pt and BQL2-Pt displayed cytotoxic activities in the micromolar range (1.3 ± 0.1 and 0.2 ± 0.2 μM, respectively) on T-24 cancer cells; however, they did not exhibit any toxicity against HL-7702 cells. They triggered T-24 cell apoptosis through a mitochondrial dysfunction pathway. BQL1-Pt and BQL2-Pt prepared from the neutral BQL1 and BQL2 ligands with cryptolepine derivatives showed better antitumor activities than 2,2′-dipicolylamine. Furthermore, BQL2-Pt effectively inhibited the growth of bladder T-24 tumor in vivo. BQL2-Pt could be a potential therapeutic candidate for cancers. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00044-021-02739-0

MEDICINAL
CHEMISTRY
RESEARCH
Medicinal Chemistry Research
https://doi.org/10.1007/s00044-021-02739-0
ORIGINAL RESEARCH
Strong in vitro and in vivo cytotoxic effects of two platinum(II)
complexes with cryptolepine derivatives
Li-Qin Qin1 Zu-Zhuang Wei2 Lin Yang1 Qi-Pin Qin1,3 Jia-Jing Zeng1 Ming-Xiong Tan1 Hong Liang3
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Received: 28 February 2021 / Accepted: 1 May 2021
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021
Abstract
Two mononuclear Pt(II) compounds, [Pt(BQL1)Cl]Cl (BQL1-Pt) and [Pt(BQL2)Cl]Cl (BQL2-Pt), with [5-(benzo[4,5]furo[3,2-
b]quinolin-11-yloxy)-pentyl]-bis-pyridin-2-ylmethyl-amine (BQL1) and [9-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-nonyl]-bis-
pyridin-2-ylmethyl-amine (BQL2), were prepared as new chemotypes for potential antitumor agents. In this study, the effects of
cryptolepine derivatives in BQL1-Pt, 2,2′-dipicolylamine Pt(II) complex, and BQL2-Pt on cellular Pt(II) accumulation,
cytotoxicity, and in vitro and in vivo antitumor activities against T-24 cancer cells and normal HL-7702 cells were evaluated.
BQL1-Pt and BQL2-Pt displayed cytotoxic activities in the micromolar range (1.3 0.1 and 0.2 0.2 μM, respectively) on T-24
cancer cells; however, they did not exhibit any toxicity against HL-7702 cells. They triggered T-24 cell apoptosis through a
mitochondrial dysfunction pathway. BQL1-Pt and BQL2-Pt prepared from the neutral BQL1 and BQL2 ligands with
cryptolepine derivatives showed better antitumor activities than 2,2′-dipicolylamine. Furthermore, BQL2-Pt effectively inhibited
the growth of bladder T-24 tumor in vivo. BQL2-Pt could be a potential therapeutic candidate for cancers.
Graphical Abstract
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Keywords Cryptolepine derivatives Pt(II) complex
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These authors contributed equally: Li-Qin Qin, Zu-Zhuang Wei
Antiproliferative activity Mitochondria damage
Supplementary information The online version contains
supplementary material available at https://doi.org/10.1007/s00044-
021-02739-0.
Introduction
* Qi-Pin Qin
qpqin2018@126.com
Among transition metal complexes, cisplatin-based com-
plexes have emerged as ubiquitous antitumor agents [1−6].
However, cisplatin-based drugs have high toxicity, low tol-
erance levels, and cause adverse reactions [7−9]. These
disadvantages have fostered the search for antiproliferative
Pt-based compounds, such as 1-methyl-7-azaindole cis- and
trans-isomers of [PtCl2(1-methyl-7-azaindole)(NH3)] [10],
[1,2-diamino-1-(4-fluorophenyl)alkanol]-dichloridoplatinum
(II) complexes [11], glycosylated Pt(IV) complexes [12],
1
College of Chemistry and Food Science, Yulin Normal University,
1303 Jiaoyudong Road, Yulin 537000, PR China
2
School of Pharmaceutical Sciences, Sun Yat-sen University, 132
Waihuan East Road, Guangzhou 510006, PR China
3
State Key Laboratory for the Chemistry and Molecular
Engineering of Medicinal Resources, School of Chemistry and
Pharmacy, Guangxi Normal University, 15 Yucai Road,
Guilin 541004, PR China

Medicinal Chemistry Research
Fig. 1 Synthesis of BQL1 and BQL2 and their respective complexes BQL1-Pt and BQL2-Pt
pyrazine Pt(II) complexes [13], bimetallic [(NHC)PtX2]2
(diamine) complexes [14], and terpyridine binuclear Pt(II)
complexes [15], which provide more effective outcomes and
have fewer side effects than cisplatin-based drugs. In parti-
cular, many researchers, including us, have focused on metal
coordination complexes bearing traditional Chinese medicine
(TCM) ligands [16−20]. It has been reported that TCM
metal complexes possesses high anticancer activity and
selectivity, and thus, many of them have been extensively
considered as ideal anticancer drugs and G-quadruplex (G4)
DNA ligands [16−26]. Unfortunately, the clinical use of
TCM metal complexes as anticancer drugs has had limited
success [16−26].
significant effects against several types of cancer cells [27
−30]. However, only two cryptolepine Zn(II) metal com-
plexes have been reported to have anticancer effects thus far
(Fig. S1) [29, 30].
Therefore, in the present study, to develop novel Pt(II)
antitumor drugs, we synthesized Pt(II) complexes with the
other quindoline derivatives. We then evaluated the char-
acteristics of two mononuclear Pt(II) compounds, [Pt
(BQL1)Cl]Cl (BQL1-Pt) and [Pt(BQL2)Cl]Cl (BQL2-
Pt) with [5-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-
pentyl]-bis-pyridin-2-ylmethyl-amine (BQL1) and [9-
(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-nonyl]-bis-pyr-
idin-2-ylmethyl-amine (BQL2), in cancer cell lines an
in vivo.
Cryptolepine and its quindoline derivatives have been
identified as G4 ligands and have been shown to have

Medicinal Chemistry Research
Table 1 The 24-h IC50 (μM) values of cryptolepine Pt complexes for
human cell lines
Notably, significant differences were observed in the anti-
tumor activities of BQL2-Pt with the BQL2 ligand and that
of BQL1-Pt bearing the BQL1 ligand. BQL2-Pt was found
to have markedly better antiproliferative activity than
BQL1, BQL2, BQL1-Pt, and cis-Pt(DMSO)2Cl2 (PtDS)
(Table 1). We speculated that the considerable differences
in the antitumor activities of BQL1-Pt and BQL2-Pt might
be a consequence of differences in their hydrocarbon chain
length. Further, the IC50 values of BQL1-Pt and BQL2-Pt
for T-24 cells were as low as 1.3 0.1 and 0.2 0.2 μM,
respectively; these values are ~6.5−100.7-fold lower than
those of cisplatin (13.2 1.3 μM), 2,2′-dipicolylamine Pt(II)
complex (20.14 1.09 μM) [21], and cryptolepine Zn(II)
metal complexes (5.92 0.35 μM) [29, 30]. More impor-
tantly, BQL1-Pt and BQL2-Pt were remarkably toxic to T-
24 cells but less toxic to normal HL-7702 cells (>100 μM).
MCF-7
SK-OV-3/
DDP
T-24
HL-7702
BQL1
28.1 1.9 62.1 1.1
4.2 0.1 3.3 0.1
23.3 0.6 51.1 1.3
1.1 0.1 1.1 0.2
39.5 0.4 >100
1.3 0.1 >100
34.0 0.9 >100
0.2 0.2 >100
BQL1-Pt
BQL2
BQL2-Pt
PtDS
>100
>100
>100
>100
cisplatin (in NaCl) 11.2 0.4 79.5 0.1
13.2 1.3 17.0 0.7
38.9 0.2 21.3 0.4
cisplatin
37.2 0.7 98.7 1.5
(in DMSO)
Results and discussion
Chemistry
Cellular distribution of the Pt(II) complexes
[5-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-pentyl]-bis-
pyridin-2-ylmethyl-amine (BQ), 2,2′-dipicolylamine Pt(II)
complex (Fig. S2), and the BQL1 ligand were synthesized
according to our previously reported procedure [21, 29, 30].
The BQL2 ligand was first synthesized through the syn-
thetic routes shown in Fig. 1, starting from 2-nitrobenzoic
acid. Further, the BQL1 and BQL2 ligands (1.0 mmol)
were obtained at 80 °C in CH3OH-DMSO solution (3.5 mL,
v-v = 34:1), after which the solid was completely dissolved
and treated with 1.0-mmol cis-Pt(DMSO)2Cl2 for 48 h to
yield the yellow solid powder of BQL1-Pt and BQL2-Pt
(yield: 82.1% and 88.4%, respectively). BQL1-Pt and
BQL1-Pt and BQL2-Pt have been shown to have excellent
cytotoxicity in previous antiproliferative activity studies, and
this may be due to their improved cellular distribution and/or
cellular uptake [36, 37]. Thus, to verify this hypothesis, we
used ICP−MS to study the intracellular Pt(II) distribution.
As shown in Table S1, the accumulation of Pt from BQL2-
Pt ((73.69 1.95 ng of Pt)/106 cells) was higher than that
from BQL1-Pt ((50.34 2.84 ng of Pt)/106 cells), cisplatin
(≤(50.00 ng of Pt)/106 cells), and other TCM metal com-
plexes [16−26]. In addition, as shown in Table S1, the
concentration of PtII inside the mitochondrial fraction that
released from BQL2-Pt ((45.02 1.45 ng of Pt)/106 cells) at
0.20 µM was higher than that released from BQL1-Pt
((20.92 2.45 ng of Pt)/106 cells) and cisplatin [16−26].
1
BQL2-Pt were fully characterized by H NMR, 13C NMR,
ESI-MS, and elemental analyses (Figs. S3−S15).
Next, the solution behavior of BQL1-Pt and BQL2-Pt
(2 × 10–5 M) in Tris-HCl buffer (containing 1.0% DMSO)
was assessed by ESI-MS and UV−vis spectroscopy. As
shown in Figs. S10 and S11, BQL1-Pt and BQL2-Pt had
peak [M-Cl]+ at m/z values of 731.9 and 788.0, respec-
tively, in Tris-HCl solution at 0 h. No change in the m/z
values was observed even after 48 h of treatment in Tris-
HCl buffer (Figs. S8 and S9), indicating that BQL1-Pt and
BQL2-Pt were stable in Tris-HCl solution. Their stabilities
were further confirmed by UV−vis spectroscopy (Fig. S16),
and the results showed that BQL1-Pt and BQL2-Pt were
stable for 48 h in Tris-HCl solution.
Antiproliferative mechanisms of Pt(II) complexes
To further understand the antiproliferative mechanism of
BQL1-Pt and BQL2-Pt, the expression of five mitochondria-
related apoptotic proteins (including caspase-3, Bcl-2, cas-
pase-9, apaf-1, and cytochrome c (cyto c)) was assessed in T-
24 cells treated with BQL1-Pt (1.3 μM) and BQL2-Pt
(0.2 μM) by western blotting. As shown in Fig. 2, BQL1-Pt
(1.3 μM) and BQL2-Pt (0.2 μM) increased the levels of cas-
pase-3, caspase-9, apaf-1, and cyto c and decreased the levels
of Bcl-2. Therefore, we assumed that BQL1-Pt and BQL2-Pt
induced apoptosis via the mitochondrial apoptosis pathway,
consequently causing DNA and mitochondrial damage (Fig. 2
and Table S2), and the order of apoptosis induction was as
follows: BQL2-Pt > BQL1-Pt > cisplatin [21, 38–40].
Biology
Cytotoxic activity of the complexes
The antiproliferative properties of BQL1, BQL2, BQL1-
Pt, and BQL2-Pt were evaluated in several malignant
(MCF-7, SK-OV-3/DDP, and T-24) and nonmalignant (HL-
7702) cell lines using the colorimetric MTT assay [31−35].
To further study whether BQL1-Pt and BQL2-Pt induced
apoptosis in T-24 cells, flow cytometry analysis was carried out.
As shown in Fig. 3A−C, BQL1-Pt and BQL2-Pt efficiently
induced apoptosis in T-24 cells, and the apoptotic values were

Medicinal Chemistry Research
Fig. 2 A Western blot analysis of the expression of apoptosis-associated proteins in T-24 cells treated with BQL1-Pt (1.3 μM) and BQL2-Pt
(0.2 μM). B Comet assay
69.35% and 80.99%, respectively, compared with those of
cisplatin at ca. 13.60% [38–40] and 2,2′-dipicolylamine Pt(II)
complex at ca. 15.04% [21]. Further, BQL2-Pt was selected for
an in vivo T-24 xenograft mouse study. When the tumors
reached a size of 80–190 mm3, the mice were randomly divided
into groups and treated with BQL2-Pt (2.0 mg/kg every 2 days)
via percutaneous injections. BQL2-Pt inhibited tumor growth
in a statistically significant manner with an inhibition ratio (IR)
of 55.3% (Tables S2−S4 and Fig. 3D); this IR was better than
that of the cryptolepine Zn metal complexes (IR = 43.0 and
50.7%) [29, 30] and cisplatin (IR = 37.1%) [16−26]. Impor-
tantly, no evident side effects such as body-weight loss
(Tables S3–S5) or death were observed in the BQL2-Pt-treated
groups.
an IC50 value of 0.2 0.2 μM, and 6.5- and 66.0-fold
higher activity than BQL1-Pt and cisplatin. BQL1-Pt and
BQL2-Pt were less toxic against normal HL-7702 cells
than cisplatin. Western blotting and cellular uptake studies
showed that BQL1-Pt and BQL2-Pt induced T-24 apop-
tosis through the mitochondrial apoptosis pathway. Fur-
ther, BQL2-Pt induced apoptosis via the endogenous
pathway and efficiently inhibited T-24 tumor xenograft
growth without any serious side effects. In summary,
BQL1-Pt and BQL2-Pt complexes bearing the neutral
cryptolepine derivatives BQL1 and BQL2 ligands showed
favorable antitumor activities.
Material and methods
Conclusion
Synthesis of compound 7
Two quindoline PtII complexes BQL1-Pt and BQL2-Pt
were prepared for the first time in this study. Among them,
BQL2-Pt showed the most potent anticancer activity, with
Compound 5 (3.00 g, 15.1 mmol, 1.00 eq) and compound 6
(3.36 g, 15.1 mmol, 1.00 eq) were added to MeCN
(30.0 mL), and then KI (2.75 g, 16.6 mmol, 1.10 eq) and

Medicinal Chemistry Research
Fig. 3 BQL1-Pt and BQL2-Pt induced T-24 cell apoptosis in vitro (A–C) and in vivo (D)
K2CO3 (3.12 g, 22.6 mmol, 1.50 eq) were added portion-
wise into the mixture at 25 °C. Next, the mixture was heated
to 75 °C and stirred at 75 °C for 16 h. TLC (petroleum ether:
ethyl acetate = 0:1, product Rf = 0.38) indicated that the
reactant was consumed completely and two new spots were
formed. The mixture was filtered to obtain a filter liquor,
and the reaction mixture was diluted with EtOAc (100 mL)
and washed with H2O (80 mL). The organic layer was
washed with H2O (50 mL) and brine (50 mL), dried over
anhydrous Na2SO4, filtered, and concentrated in vacuo to
Synthesis of [9-(benzo[4,5]furo[3,2-b]quinolin-11-
yloxy)-nonyl]-bis-pyridin-2-ylmethyl-amine (BQL2)
Compound 7 (1.00 g, 2.93 mmol, 1.20 eq) was added to
DMA (10.0 mL), and then NaH (195 mg, 4.88 mmol, 60%
purity, 2.00 eq) was added portion-wise into the mixture at
25 °C. The mixture was then stirred at 25 °C for 0.2 h, and
then BQ (619 mg, 2.44 mmol, 1.00 eq) was added at 25 °C.
Next, the mixture was heated to 70 °C and stirred for 1.5 h.
LC-MS showed that compound BQ was utilized com-
pletely, and one main peak was observed with desired m/z.
In addition, TLC (petroleum ether:ethyl acetate = 1:1, pro-
duct Rf = 0.43) results showed that the reactant was con-
sumed completely and two new spots were observed. The
mixture was quenched with saturated NH4Cl (100 mL) and
extracted with EtOAc (150 mL × 2). The organic phases
were washed with water (80 mL × 3), dried using Na2SO4,
and filtered and concentrated in vacuum. The residue was
purified using column chromatography (SiO2, petroleum
1
obtain a brown oil. ESI-MS and H NMR were used to
confirm that the brown oil was compound 7 (5.00 g,
1
11.5 mmol, 76.3% yield). H NMR (400 MHz, chloroform-
d): δ 8.55–8.45 (m, 2H), 7.64 (td, J = 7.7, 1.7 Hz, 2H), 7.53
(d, J = 7.8 Hz, 2H), 7.16–7.09 (m, 2H), 3.79 (s, 4H), 3.62 (t,
J = 6.6 Hz, 2H), 2.54–2.49 (m, 2H), 1.56–1.49 (m, 4H),
1.33–1.21 (m, 10H). ESI-MS: m/z = 342.1 for [M + H]+.
Elemental analysis: calcd (%) for C21H31N3O: C 73.86, H
9.15, N 12.30; found: C 73.85, H 9.17, N 12.29.

Medicinal Chemistry Research
ether:ethyl acetate = 50:1 to 1:1) and evaporated to obtain
the desired product. ESI-MS, 1H NMR, and 13C NMR
studies indicated that BQL2 (2.60 g, 4.46 mmol, 61.0%
yield, 95.9% purity) was obtained as a brown oil. 1H NMR:
(400 MHz, CDCl3-d) δ 8.48 (br d, J = 4.4 Hz, 2H), 8.35 (t,
J = 9.2 Hz, 2H), 8.18 (d, J = 8.6 Hz, 1H), 7.68 (dt, J = 1.3,
7.7 Hz, 1H), 7.64–7.57 (m, 3H), 7.55–7.46 (m, 3H),
7.46–7.38 (m, 1H), 7.10 (dd, J = 5.5, 6.6 Hz, 2H), 4.94 (t, J
= 6.5 Hz, 2H), 3.78 (s, 4H), 3.47 (s, 1H), 2.57–2.44 (m,
2H), 2.02–1.87 (m, 2H), 1.65–1.44 (m, 4H), 1.42–1.32 (m,
2H), 1.32–1.19 (m, 6H). 13C NMR: (101 MHz, CDCl3-d) δ
160.12, 158.63, 149.15–148.75 (m, 1 C), 147.29, 144.22,
136.37, 134.48, 130.59, 128.48 (d, J = 5.9 Hz, 1 C),
124.75, 123.48, 123.11, 122.84, 122.37 (d, J = 18.3 Hz, 1
C), 121.85, 121.38, 111.97, 72.95, 60.48, 54.53, 50.57,
30.09, 29.63–29.17 (m, 1 C), 27.19 (d, J = 24.9 Hz, 1 C),
25.91. ESI-MS: m/z = 559.3 for [M + H]+. Elemental ana-
lysis: calcd (%) for C36H38N4O2: C 77.39, H 6.86, N 10.03;
found: C 77.38, H 6.88, N 10.02.
Data for BQL2-Pt
Yield: 88.4%. ESI-MS: m/z = 788.0 for [M-Cl]+ ([Pt(BQL2)
Cl]+, 10 mM pH 7.35 Tris-HCl buffer solution, 5% DMSO).
Elemental analysis: calcd (%) for C36H38Cl2N4O2Pt: C 52.43,
1
H 4.64, N 6.79; found: C 52.42, H 4.67, N 6.78. H NMR
(500 MHz, DMSO-d6) δ 8.79 (dt, J = 6.0, 1.8 Hz, 2H),
8.32–8.24 (m, 4H), 8.17–8.11 (m, 1H), 7.83 (d, J = 7.9 Hz,
2H), 7.80–7.72 (m, 3H), 7.68–7.65 (m, 2H), 7.55 (dddd, J =
30.5, 8.0, 6.9, 1.2 Hz, 2H), 5.39 (d, J = 15.7 Hz, 2H),
4.95–4.81 (m, 4H), 3.03–2.98 (m, 2H), 1.84 (dq, J = 13.6,
6.7 Hz, 2H), 1.46 (q, J = 10.9, 7.2 Hz, 4H), 1.25 (t, J =
7.2 Hz, 2H), 1.16–1.07 (m, 6H). 13C NMR (126 MHz,
DMSO-d6) δ 166.36, 158.56, 149.47, 148.80, 147.24, 143.78,
141.78, 134.38, 131.72, 129.10, 128.95, 125.81, 125.57,
124.39, 123.93, 122.90, 122.49, 122.28, 121.20, 112.86,
73.06, 68.33, 64.68, 40.94, 40.53, 40.36, 40.20, 40.03, 39.86,
39.69, 39.53, 29.81, 29.09, 29.06, 28.90, 27.44, 26.24, 25.69.
Methods
Synthesis of BQL1-Pt and BQL2-Pt
A total of 1.0-mM cisplatin was prepared in 0.154-M NaCl
and DMSO solution [19]. For details on the methods and
materials used for BQL1-Pt (1.3 μM) and BQL2-Pt
(0.2 μM) preparation, please refer to the published meth-
ods of Qin, Liang, and Gou [29, 36]. In addition, detailed
procedures for other experimental methods are described in
the supplementary information.
The BQL1 or BQL2 ligand (1.0 mmol) and 1.0-mmol cis-
Pt(DMSO)2Cl2 were first dissolved in CH3OH-DMSO
solution (3.5 mL, v-v = 34:1) at 80 °C for 48 h, and the
final reaction mixture was allowed to cool overnight. After
filtration, the final solution was allowed to stand at 30 °C
for about 2 days, and the yellow solid powder suitable for
structural characterization was isolated, washed with
ethanol (EtOH) and diethyl ether, and air-dried.
Acknowledgements We thank the National Natural Science Founda-
tion of China (21867017) and the Natural Science Foundation of
Guangxi (2020GXNSFAA297077).
Data for BQL1-Pt
Compliance with ethical standards
Yield: 82.1%. ESI-MS: m/z = 731.9 for [M-Cl]+ ([Pt
(BQL1)Cl]+, 10 mM pH 7.35 Tris-HCl buffer solution,
5% DMSO). Elemental analysis: calcd (%) for
C32H30Cl2N4O2Pt: C 50.01, H 3.93, N 7.29; found: C
Conflict of interest The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
1
50.00, H 3.95, N 7.28. H NMR (500 MHz, DMSO-d6) δ
8.76 (dd, J = 5.8, 1.6 Hz, 2H), 8.29–8.22 (m, 3H), 8.20
(dd, J = 8.9, 1.2 Hz, 1H), 8.14–8.10 (m, 1H), 7.79 (d, J =
7.9 Hz, 2H), 7.78–7.72 (m, 3H), 7.65–7.60 (m, 2H), 7.57
(ddd, J = 8.2, 6.7, 1.2 Hz, 1H), 7.53 (ddd, J = 7.9, 6.5,
1.5 Hz, 1H), 5.41 (d, J = 15.9 Hz, 2H), 4.89 (d, J =
15.8 Hz, 2H), 4.79 (t, J = 6.1 Hz, 2H), 3.15–3.07 (m, 2H),
1.77 (dq, J = 12.2, 6.3 Hz, 2H), 1.65 (dq, J = 13.8, 7.1 Hz,
2H), 1.51 (q, J = 7.8 Hz, 2H). 13C NMR (126 MHz,
DMSO-d6) δ 166.34, 158.54, 149.44, 148.79, 147.20,
143.63, 141.73, 134.33, 131.75, 129.11, 128.93, 125.76,
125.61, 124.41, 123.91, 122.87, 122.51, 122.30, 121.12,
112.87, 72.78, 68.29, 64.57, 40.92, 40.51, 40.34, 40.18,
40.01, 39.84, 39.68, 39.51, 29.47, 27.13, 22.94.
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