Synthesis and Investigation of Copper Complexes with Selected Azomethine Monobenzo Crown Ether Derivatives

Article abstract of DOI:10.1134/S1070363219030125

A series of novel azomethine derivatives of benzo-18-crown-6, benzo-15-crown-5, and aniline as well as their complexes with copper(II) acetate have been synthesized. Using the MTT assay, the antitumor activity of the obtained compounds has been determined

Full text of DOI:10.1134/S1070363219030125

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 3, pp. 440–445. © Pleiades Publishing, Ltd., 2019.
Russian Text © N.Yu. Sadovskaya, V.N. Glushko, M.A. Baryshnikova, D.A. Afanasyeva, M.Yu. Zhila, S.K. Belus, 2019, published in Zhurnal Obshchei
Khimii, 2019, Vol. 89, No. 3, pp. 412–418.
Synthesis and Investigation of Copper Complexes with Selected
Azomethine Monobenzo Crown Ether Derivatives
N. Yu. Sadovskayaa, V. N. Glushkoa*, M. A. Baryshnikovaa, D. A. Afanasyevaa,
M. Yu. Zhilaa, and S. K. Belusa
a The Federal State Unitary Enterprise “Institute of Chemical Reagents and High Purity Chemical Substances of National
Research Centre “Kurchatov Institute,” Bogorodskii Val 3, Moscow, 107076 Russia
*e-mail: tetrazoli@yandex.ru
Received October 11, 2018; revised October 23, 2018; accepted October 25, 2018
Abstract—A series of novel azomethine derivatives of benzo-18-crown-6, benzo-15-crown-5, and aniline as
well as their complexes with copper(II) acetate have been synthesized. Using the MTT assay, the antitumor
activity of the obtained compounds has been determined. The effect of individual structural elements on the
antitumor activity of the whole compound has been assessed.
Keywords: crown ethers, copper complexes, the Schiff’s bases, pyridinecarboxaldehyde, antitumor activity,
MTT assay
DOI: 10.1134/S1070363219030125
Crown ethers are macroheterocyclic compounds
which find important applications in different areas of
science and technology. The interest to crown ethers is
due to their unique ability for selective complexing
allowing their use as catalysts of interphase transfer in
organic synthesis, selective extracting agent for metals
in mineral resource industry, and separation of
radionuclides [1]. The investigations of biological and
medical potential of crown ethers and their complexes
with metals have been numerous. Crown ethers are
well-known ionophores and can exhibit antibacterial or
antifungal activity [2–4]. Nowadays, the studies on the
use of crown ethers derivatives as active compounds
for chemotherapy of tumors, carriers of drugs to cancer
cell, and photosensitizers have become topical [5–8]. It
has been confirmed that copper, cobalt, nickel,
palladium, and ruthenium complexes with organic
ligands can cause apoptosis of cancer cells [9–12].
ketones with primary amines. Azomethine derivatives
of crown ethers, for example, benzo-15-crown-5, have
been described earlier [14, 15]. 4-Aminobenzo-15-
crown-5 and 2-hydroxy-4-methoxybenzaldehyde or 2-
hydroxy-5-methoxybenzaldehyde have been used as
the starting compounds. The synthesis of these imines
has been carried out in methanol or anhydrous
chloroform medium [16].
Herein we synthesized novel derivatives of crown
ethers and their copper complexes and investigated
cytotoxicity and antitumor activity of the prepared
compounds.
At the first stage of the study, we obtained azo-
methine derivatives of benzo-15-crown-5 1 [N-(pyridin-
4-ylmethyleneamino)benzo-15-crown-5 1a, N-(pyridin-
3-ylmethyleneamino)benzo-15-crown-5 1b], benzo-18-
crown 6 2 {N-(pyridin-4-ylmethyleneamino)benzo-18-
crown-6 2a, N-(pyridin-3-ylmethyleneamino)benzo-18-
crown-6 2b [17, 18]}, and aniline 3 [N-(pyridin-4-
ylmethyleneamino)aniline 3a, N-(pyridin-3-ylmethyl-
eneamino)aniline 3b]. Investigations of aniline
derivatives which did not contain a crown ring gave an
estimation of the influence of that structural fragment
on antitumor activity. The Schiff’s bases were obtained
via condensation of 4-pyridinecar-boxyaldehyde 4 or 3
-pyridinecarboxyaldehyde 5 with the corresponding
Crown-containing imines are the most interesting,
in particular, pyridinylmethyleneaminobenzo crown
ethers and their complexes which may be used in
medicine, agriculture, and other fields because of their
strongly selective sensor properties to metal cations
[13].
The general method of preparation azomethines (imines,
the Schiff’s bases) is the condensation of aldehydes or
440

SYNTHESIS AND INVESTIGATION OF COPPER COMPLEXES
441
Scheme 1.
N R
N R
O
(CH3COO)2Cu
RNH2
+
+
Cu(CH3COO)2
N
N
N
4
1a−3a
N R
N R
O
N
(CH3COO)2Cu
RNH2
N
N
Cu(CH3COO)2
1b−3b
5
O
O
O
*
*
O
O
O
O
*
O
O
R =
O
(1),
(2),
(3).
O
crown ethers 1, 2 or aniline 3 in ethanolic medium at
the aldehyde : crown ether molar ratio = 1.2 : 1.0
(Scheme 1). Copper complexes of the mentioned
compounds were prepared via the addition of a
methanolic solution of copper acetate to equimolar
amount of the corresponding azomethine with further
keeping at heating.
protons at the С3 and С5 atoms. The assignment of the
protons in compound 2a was performed similarly. As
for the meta-substituted pyridine fragment, doublet of
doublets at 7.54 ppm corresponded to the proton at the
С5 atom, doublet of triplets at 8.28 ppm corresponded
to the proton at the С6 atom, doublet of doublets at
8.68 ppm corresponded to the proton at the С4 atom,
and doublet at 9.03 ppm corresponded to the proton at
the С9 atom. The atoms numbering is given in Scheme 2.
The composition and structure of the prepared
Schiff’s bases were determined using the data of
elemental analysis as well as NMR and IR
spectroscopy. The assignment of the signals was based
The investigation of cytotoxicity was carried out
using five cell lines of human tumors: colon carcinoma
HCT-116, prostate carcinoma РС-3, lung carcinoma
А549, mammary adenocarcinoma MCF-7, and T cell
lymphoblastic leukemia Jurkat, obtained from Cell
lines bank of Blokhin National Research Center of
Oncology. The MTT assay was used for the estimation
of the antitumor activity [19].
1
on the 1D and 2D spectroscopy data (COSY and Н–
1
13С HSQC). The Н NMR spectra of the compounds
containing crown ether fragment contained
characteristic signals of the СН2 groups and the
aromatic ring protons. For example, the spectrum of
compound 1b contained doublet of doublets at 6.91
ppm corresponding to the proton at the С9 carbon atom
along doublets at 7.00 and 7.04 ppm corresponding to
protons at the С12 and С9 carbon atoms, respectively.
Eight compounds of the prepared 12 ones exhibited
antitumor activity: 3a, 2a, 3a-Cu(CH3COO)2, 1a-Cu
(CH3COO)2, 2a-Cu(CH3COO)2, 3b-Cu(CH3COO)2, 1b-
Cu(CH3COO)2, and 2b-Cu(CH3COO)2. The degree of
inhibition of the cells growth is given in the Table. The
obtained data showed that the copper complexes of the
prepared ligands exhibited cytotoxic activity, but free
ligands (pyridine-containing azomethine crown ethers)
were inactive towards the used cell lines, except for the
ligand 2a containing 18-membered crown ether cycle,
1
The Н NMR spectra of the compounds containing
para-substituted pyridine fragment showed two weak-
field signals corresponding to protons at the С2, С6
(multiplet, 7.79–7.85 ppm for compound 1a) and С3,
С5 (multiplet, 8.68–8.77 ppm) carbon atoms. Accord-
ing to the data of HSQC spectroscopy, the signal of the
proton at the С7 atom was overlapped with those of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 3 2019

442
SADOVSKAYA et al.
Scheme 2.
O
O
5C
5C
6
6
C
C
4C
O
O
N
O
O
C7
N
C7
N
9C
9C
3C
N
C2
C2
O
O
O
O
13C
13C
C12
1a
C12
1b
which was active against T cell lymphoblastic
leukemia Jurkat and inhibited the growth of cancer
cells by 58%.
obtained from 4-pyridincarboxyaldehyde. It was
figured out that the copper complexes containing 15-
membered crown ring exhibited lower activity than the
18-membered ones. The copper complexes with
Schiff’s bases (aniline derivatives) were intermediate
between the complexes containing 15- and 18-
membered crown rings. Hence, the activity of the
copper complexes synthesized from azomethine
derivatives of amino crown ethers and aniline was
increased in the 1 < 3 < 2 series.
The in vitro investigation revealed certain structure–
property relationships for the considered crown-
containing Schiff’s bases and their copper complexes.
Generally, the free ligands did not exhibit cytotoxic
activity, except for compounds 3a and 2a which were
active against the Jurkat line. The prepared copper
complexes were active, and their activity depended on
their structural features. It was shown that meta and
para substitution of the pyridine structural fragment
affected the activity of the copper complexes,
however, the clear dependence was not observed. In
the case of 18-membered cycles, the most active one
was the copper complex obtained from 3-
pyridinecarboxyaldehyde. In the case of 15-membered
cycles, the most active one was the copper complex
In summary, novel azomethine derivatives of crown
ethers and copper complexes based on them which can
have wide implications, in particular in medicine were
prepared. We showed that the complex based on N-
(pyridin-3-ylmethynenamino)benzo-18-crown-6 exhibited
the highest cytotoxic activity, inhibiting the growth of
cell lines of human tumors by 77–86%.
EXPERIMENTAL
Inhibition of cells growth of the human tumors of cell lines
by compounds 1a–3b and their copper complexes
1
The H NMR spectra were registered in DMSO-d6
at 25°С using a Bruker AVANCE III NanoBay device
operating at 300.28 MHz. Elemental analysis was
performed using an Eurovector EuroEA 3000 СНNS-
analyzer. The ATR IR spectra were recorded using a
FTIR VERTEX 70 spectrometer (600–3800 cm–1 with
resolution 4 cm–1; ZnSe crystal).
I, %
Comp. no.
РС-3 MCF-7 А549 НСТ-116 Jurkat
1a
1b
2a
2b
3a
3b
8
20
1
16
–2
1
14
9
39
–2
10
4
44
19
58
24
58
24
60
35
89
86
87
42
Synthesis of the Schiff’s bases. 0.012 mol of the
corresponding aldehyde 5 or 4 was added dropwise to
a solution of 0.01 mol of aniline 3 or crown ether 1 or
2 in 10 mL of ethanol. The obtained mixture was kept
at 40°С for 3 h and then evaporated off. The
precipitate was filtered off and dried in air at room
temperature.
8
17
17
8
2
11
25
17
54
53
65
84
73
62
18
17
65
53
80
85
77
60
7
13
15
12
26
77
29
18
1a-Cu(CH3COO)2 50
1b-Cu(CH3COO)2 46
2a-Cu(CH3COO)2 68
2b-Cu(CH3COO)2 77
3a-Cu(CH3COO)2 71
3b-Cu(CH3COO)2 50
N-(Pyridin-4-ylmethylenamino)benzo-15-crown-5
(1a). Yield 86%, light-green powder, mp 75.1–76.0°С.
IR spectrum, ν, cm-–1: 627 w, 814 w, 851 w, 934 w,
989 w, 1050 m, 1091 m, 1131 s (C–O–C), 1230 s,
1266 s, 1316 m, 1363 w, 1414 w, 1453 m, 1513 s,
1555 w, 1588 m, 1598 m, 1626 w (C=N), 2868–2922
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 3 2019

SYNTHESIS AND INVESTIGATION OF COPPER COMPLEXES
443
1
br. s (C–H), 3030–3060 br. w (С–НAr). Н NMR
spectrum, δ, ppm: 3.62 br. s (8Н, СН2), 3.75–3.82 m
(4Н, СН2), 4.05–4.16 m (4Н, СН2), 6.96 d. d (1Н, СН,
J = 8.5, 2.2 Hz), 7.01 d (1H, CH, J = 8.5 Hz), 7.08 d
(1H, CH, J = 2.2 Hz), 7.79–7.85 m (2H, CH), 8.68–
8.77 m (3Н, СН + HC=N). Found, %: С 64.69; Н 6.57;
N 7.58. C20H24N2O5. Calculated, %: С 64.50; Н 6.53;
N 7.52.
4.07–4.18 m (4Н, СН2), 6.91 d. d (1Н, СН, J = 8.5,
2.3 Hz), 7.00 d (1Н, СН, J = 8.5 Hz), 7.04 d (1Н, СН,
J = 2.4 Hz), 7.53 d. d (1Н, СН, J = 7.9, 4.7 Hz), 8.28
d. t (1Н, СН, J = 7.9, 1.9 Hz), 8.68 d. d (1Н, СН, J =
4.7, 1.4 Hz), 8.75 s (1Н, НС=N), 9.03 d (1Н, СН, J =
1.0 Hz). Found, %: С 63.61; Н 6.62; N 6.32.
C22H28О6N2. Calculated, %: С 63.45; Н 6.77; N 6.27.
N-(Pyridin-4-ylmethylenamino)aniline (3a). Yield
92%, white powder, mp 67.8–69.2°С. IR spectrum, ν,
cm–1: 649 m, 690 s, 734 m, 764 s, 819 s, 881 w, 913 m,
961 w, 977 w, 987 w, 1022 w, 1059 w, 1074 w, 1165
w, 1186 w, 1209 w, 1226 w, 1236 w, 1284 w, 1325 m,
1364 w, 1411 s (Py), 1449 w, 1482 m (Py), 1554 w,
1579 w (Py), 1593 m (Py), 1620 m (С=N), 1671 m,
1711 m, 1799 w, 1881 w, 1953 w, 2001 w, 2884 w
(С–Н), 2991 w (С–Н), 3025 w (С–НAr), 3054 w (С–
N-(Pyridin-3-ylmethylenamino)benzo-15-crown-5
(1b). Yield 88%, light-green powder, mp 87.3–88.0°С.
IR spectrum, ν, cm–1: 623 w, 705 w, 811 w, 844 w, 918
w, 939 w, 991 w, 1050 w, 1091 w, 1129 s (C–O–C),
1142 s, 1237 m, 1262 s, 1331 w, 1373 w, 1421 w,
1449 w, 1510 s, 1568 w, 1586 w, 1625 w (C=N), 2873–
1
2930 br. s (C–H), 3030–3060 br. w (С–НAr). Н NMR
spectrum, δ, ppm: 3.63 br. s (8Н, СН2), 3.75–3.82 m
(4Н, СН2), 4.04–4.15 m (4Н, СН2), 6.91 d. d (1Н, СН,
J = 8.4, 2.3 Hz), 7.00 d (1H, CH, J = 8.4 Hz), 7.04 d
(1H, CH, J = 2.3 Hz), 7.54 d. d (1Н, СН, J = 7.9,
4.8 Hz), 8.28 d. t (1Н, СН, J = 7.9, 1.7 Hz), 8.68 d. d
(1Н, СН, J = 4.8, 1.7 Hz), 8.75 s (1Н, НС=N), 9.03 d
(1H, CH, J = 1.7 Hz). Found, %: С 64.51; Н 6.57; N
7.61. C20H24N2O5. Calculated, %: С 64.50; Н 6.53; N 7.52.
1
НAr), 3072 w (С–НAr). Н NMR spectrum, δ, ppm:
7.29–7.37 m (3Н, СН), 7.41–7.50 m (2Н, СН), 7.83–
7.88 m (2Н, СН), 8.69 s (1Н, НС=N), 8.76 d (1H, CH,
J = 3.4 Hz). Found, %: С 78.99; Н 5.57; N 15.58.
C12H10N2. Calculated, %: С 79.10; Н 5.53; N 15.37.
N-(Pyridin-3-ylmethylenamino)aniline (3b). Yield
93%, yellow oil. IR spectrum, ν, cm–1: 620 w, 667 w,
693 s, 760 s, 804 m, 830 w, 874 m, 910 w, 977 w,
1023 w, 1074 w, 1092 v.w, 1114 v.w, 1186 w, 1204 m,
1236 w, 1324 m, 1365 w, 1386 v.w, 1418 m (Py),
1450 w, 1485 m (Py), 1570 m (Py), 1587 m (Py), 1626
m (С=N), 1703 m, 1943, 2857 w (С–Н), 2886 w (С–
Н), 3001 w (С–НAr), 3031 w (С–НAr), 3054 w (С–
N-(Pyridin-4-ylmethylenamino)benzo-18-crown-6
(2a). Yield 89%, light-green powder, mp 63.9–64.7°С.
IR spectrum, ν, cm–1: 629 w, 713 m, 802 m, 829 m,
849 m, 899 w, 933 m, 949 m, 984 m, 1032 m, 1056 m,
1116 s (С–О–С), 1189 w, 1222 m, 1258 m (С–Н),
1319 w, 1359 w, 1414 w, 1457 w (Py), 1482 w (Py),
1509 s (СН2), 1587 w (Py), 1624 w (С=N), 2855 br,
2925 w (С–Н), 2932 w (С–Н), 3030 w (С–НAr), 3055
1
НAr), 3080 w (С–НAr). Н NMR spectrum, δ, ppm:
7.26–7.33 m (3Н, СН), 7.39–7.48 m (2Н, СН), 7.54 d.
d (1Н, СН, J = 7.9, 4.6 Hz), 8.31 d. t (1Н, СН, J = 7.9,
1.9 Hz), 8.67–8.73 m (2Н, НС=N + СН), 9.06 d (1Н,
СН, J = 1.9 Hz). Found, %: С 78.89; Н 5.56; N 15.58.
C12H10N2. Calculated, %: С 79.10; Н 5.53; N 15.37.
1
w (С–НAr). Н NMR spectrum, δ, ppm: 3.52 s (4H,
СН2), 3.55–3.64 m (8Н, СН2), 3.73–3.80 m (4Н, СН2),
4.07–4.18 m (4Н, СН2), 6.95 d. d (1Н, СН, J = 8.5,
2.0 Hz), 7.01 d (1Н, СН, J = 8.5 Hz), 7.08 d (1Н, СН,
J = 2.0 Hz), 7.82 d (2Н, СН, J = 5.8 Hz), 8.68–8.77 m
(3Н, СН + НС=N). Found, %: С 63.31; Н 6.81; N
6.58. C22H28N2О6. Calculated, %: С 63.45; Н 6.77; N 6.73.
General procedure for preparation of complexes
with Schiff bases 1a–3b. A solution of 0.001 mol of
the corresponding Schiff’s base in 10 mL of methanol
was added to a solution of 0.001 mol of copper(II)
acetate in 15 mL of methanol. The obtained mixture
was kept at 45°С for 4 h. The precipitate was filtered
off and dried in air at room temperature.
N-(Pyridin-3-ylmethylenamino)benzo-18-crown-6
(2b). Yield 89%, light-green powder, mp 73.9–74.2°С.
IR spectrum, ν, cm–1: 629 w, 713 m, 802 m, 829 m,
849 m, 899 w, 933 m, 949 m, 984 m, 1032 m, 1056 m,
1116 s (С–О–С), 1189 w, 1222 m, 1258 m (С–Н),
1319 w, 1359 w, 1414 w, 1457 w (Py), 1482 w (Py),
1509 s (СН2), 1587 w (Py), 1624 w (С=N), 2855 br,
2925 w (С–Н), 2932 w (С–Н), 3030 w (С–НAr), 3055
w (С–НAr). 1Н NMR spectrum, δ, ppm: 3.53 br. s (4Н,
СН2), 3.55–3.61 m (8Н, СН2), 3.74–3.80 m (4Н, СН2),
Complex 1a-Cu(CH3COO)2. Yield 94%, green
powder, mp 203.2–203.8°С (decomp.). IR spectrum
(KBr), ν, cm–1: 617 s, 628 s, 680 s, 792 w, 831 w, 890
s, 942 m, 974 w, 1012 w, 1026 m, 1053 m, 1084 w,
1120 s (C–O–C), 1142 s, 1202 w, 1276 m (C–HAr),
1301 m, 1350 w, 1418 s, 1432 s, 1508 s, 1608 s
(COOCu), 1628 s (C=N), 2869–2930 br. m (C–H).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 3 2019

444
SADOVSKAYA et al.
Found, %: С 52.12; Н 5.51; N 5.14. C24H30N2О9Cu.
Calculated, %: С 52.02; Н 5.46; N 5.06.
fetal bovine serum, 10 mM HEPES (Sigma, USA),
2 mM of L-glutamine (Sigma, USA), 40 ng/mL of
gentamicin (ICN, USA), amino acids, sodium
pyruvate, and vitamin solution (PanEko, Russia) at
37°С under atmosphere containing 5% of СО2. The
cells were kept in logarithmic growth phase via
continuous passage every 3–4 days. Versene solution
was used for detachment of the cultures from plastic.
Complex 1b-Cu(CH3COO)2. Yield 91%, green
powder, mp 208.9–210.0°С (decomp.). IR spectrum, ν,
cm–1: 628 s, 641 s, 682 s, 713 m, 803 m, 822 m, 841
m, 887 m, 929 w, 980 m, 1031 w, 1052 m, 1080 m,
1137 s (C–O–C), 1191 w, 1237 m, 1262 m, 1316 w,
1428 s, 1513 s, 1610 s (COOCu), 1629 s (C=N), 2870–
2950 br. w (C–H). Found, %: С 53.06; Н 5.51; N 5.12.
C24H30N2О9Cu. Calculated, %: С 53.03; Н 5.46; N
5.06.
For the MTT assay, the cells were distributed in 96-
well flat-bottom plates (Costar, USA). The inves-
tigated compounds in concentration 100 µM were
added to each well after one day and incubated with
cells for 72 h in 5% СО2 at 37°C. Each compound was
tested in triplicate. The compounds were dissolved in
DMSO so that the DMSO concentration in a well did
not exceed 1%. The wells with cells and 1% of DMSO
in solid growth medium were used as reference. 20 µM
of the МТТ solution (final concentration 1 µg/mL) was
added to each well after 72 h and incubated for 4 h at
37°С in 5% CO2. After the formation of formazan, the
supernatant was removed, and the precipitate was
dissolved in 150 µL of DMSO. Then the plates were
placed in a thermostat for 10 min at 37°С and then
shaken for uniform dissolution of the formazan
crystals. Then the intensity of medium coloration was
measured using an AIFR-01 Uniplan photometrical
analyzer of immunoenzymatic reactions (Pikon) at λ =
540 nm. The absorption was directly proportional to
the number of alive cells.
Complex 2a-Cu(CH3COO)2. Yield 88%, green
powder, mp 223.2–223.9°С (decomp.). IR spectrum, ν,
cm–1: 627 w, 793 m, 819 m, 839 w, 862 w, 879 w, 945
m, 987 m, 1049 m, 1107 s, 1127 s (С–О–С), 1225 s,
1245 m, 1265 s, 1315 w, 1326 w, 1354 w, 1412 w,
1427 w, 1449 w (Py), 1463 w (Py), 1511 s (СН2), 1552
v.w, 1582 m (Py), 1598 m (С=N), 2868 m (С–Н),
2923 w (С–Н), 3030 w (С–НAr), 3056 w (С–НAr).
Found, %: С 52.30; Н 5.81; N 4.57. C26H34N2О10Cu.
Calculated, %: С 52.22; Н 5.73; N 4.69.
Complex 2b-Cu(CH3COO)2. Yield 88%, green
powder, mp 230.1–230.9°С (decomp.). IR spectrum
(KBr), ν, cm–1: 628 w, 642 w, 680 s, 702 m, 811 m,
855 w, 948 m, 993 m, 1031 w, 1052 m, 1120 s, 1223
m, 1257 m, 1297 w, 1333 w, 1354 w, 1371 w, 1426 s,
1443 m, 1510 m, 1587 w, 1616 s, 2866 br, 2923 br,
3032 w, 3050 w. Found, %: С 52.33; Н 5.61; N 4.53.
C26H34N2О10Cu. Calculated, %: С 52.22; Н 5.73; N 4.69.
The degree of inhibition of the cell growth (I, %)
Complex 3a-Cu(CH3COO)2. Yield 91%, green
powder, mp 236.2–236.8°С (decomp.). IR spectrum
(KBr), ν, cm–1: 631 m, 660 m, 683 s, 735 w, 768 m,
824 m, 883 w, 913 w, 961 w, 976 w, 1013 w, 1033 w,
1056 w, 1185 w, 1211 w, 1244 w, 1320 w, 1350 w,
1418 s, 1433 s, 1484 w, 1559 w, 1607 s, 1624 s, 2885
w, 3000 w, 3061 w. Found, %: С 52.61; Н 4.51; N 7.57.
C16H16N2О4Cu. Calculated, %: С 52.82; Н 4.43; N 7.70.
was determined as follows:
D0
× 100%,
1 −
I =
Dr
where Dr is absorbance in reference wells, D0 is
absorbance in the specimen wells. A compound was
considered cytostatically active if it caused the
inhibition of cell growth by more than 50%.
Complex 3b-Cu(CH3COO)2. Yield 89%, green
powder, mp 239.1–240.0°С (decomp.). IR spectrum, ν,
cm–1: 627 w, 643 w, 681 s, 699 m, 761 w, 800 w, 892
w, 988 w, 1029 w, 1049 w, 1074 v.w, 1100 v.w, 1124
v.w, 1186 w, 1197 w, 1244 w, 1327 w, 1384 w, 1374
w, 1417 s, 1427 s, 1471 w, 1488 w, 1578 m, 1617 s,
2930 w, 3007 w, 3071 w. Found, %: С 52.73; Н 4.51;
N 7.62. C16H16N2О4Cu. Calculated, %: С 52.82; Н
4.43; N 7.70.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
REFERENCES
1. Glagolev, Yu.V., Logunov, M.V., Mamakin, I.V.,
Polosin, V.M., Rovnyi, S.I., Starchenko, V.A., Shishe-
lov, Yu.P., and Yakovlev, N.G, RU Patent no. 2318258,
2008.
Biological experiments. The cell lines were
cultivated in RPMI-1640 medium containing 10% of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 3 2019

SYNTHESIS AND INVESTIGATION OF COPPER COMPLEXES
445
2. Deshmukh, M.B., Alasundkar, K.N., Salunkhe, D.K.,
and Sankpal, S.A., J. Chem. Pharm. Res., 2010, vol. 2,
no. 4, p. 437. doi 10.1007/s10847-005
Tretyakova, A.V., Zyk, N.V., Zefirov, N.S., Kabanov, A.V.,
and Dontsova, O.A., J. Med. Chem., 2014, vol. 57,
no. 14, p. 6252. doi 10.1021/jm500154f
10. Iakovidis, I., Delimaris, I., and Piperakis, S.M., Mol.
Bio. Int., 2011, vol. 2011, p. 1. doi 10.4061/
2011/594529
11. Marzano, C., Pellei, M., Tisato, F., and Santini, C., Anti-
Cancer Agents Med.Chem., 2009, vol. 9, no. 2, p. 185.
doi 10.2174/187152009787313837
12. Plotek, M., Dudek, K., and Kyziol, A., Chemik., 2013,
vol. 67, no. 12, p. 1181.
13. Usacheva, T.R., Cand. Sci. (Chem.) Dissertation,
Ivanovo, 2016.
14. Dorokhov, A.V., Cand. Sci. (Chem.) Dissertation,
Moscow, 2007.
15. Timonin, A.N., Cand. Sci. (Chem.) Dissertation,
Moscow, 2011.
16. Guler, H., Hayvali, Z., Dal, H., and Hokelek, T.,
Polyhedron, 2012, vol. 31, no. 1, p. 688. doi 10.1016/
j.poly.2011.10.034
17. Glushko, V.N. and Sadovskaya, N.Yu., RU Patent
no. 2655166, 2018.
3. Alfonso, I. and Quesada, R., Chem. Sci., 2013, vol. 4,
no. 8, p. 3009. doi 10.1039/C3SC50882J
4. Huang Sh.-T., Kuo, H.-S., Hsiao Ch.-L., and Lin, Yu.-L.,
Bioorg. Med. Chem., 2002, vol. 10, no. 6, p. 1947. doi
10.1016/S0968-0896(02)00004-4
5. Supek, F., Ramljak, T.S., Marjanovic, M., Buljubasic, M.,
Kragol, G., Llic, N., Smuc, T., Zahradka, D., Mlinaric-
Majerski, K., and Kralj, M., Eur. J. Med. Chem., 2011,
vol. 46, no. 8, p. 3444. doi 10.1016/j.ejmech.2011.05.009
6. Karawajew, L., Glibin, E.N., Maleev, V.Y., Czerwony, G.,
Dörken, B., Davies, D.B., and Veselkov, A.N., Anti-
Cancer Drug Des., 2000, vol. 15, no. 5, p. 331.
7. Jansen, B.A.J.,Wielaard, P., den Dulk, H., Brouwer, J.,
and Reedijk, J., Eur. J. Inorg. Chem., 2002, no. 9,
p. 2375. doi 10.1002/1099-0682(200209)
2002:9<2375::AID-EJIC2375>3.0.CO;2-B
8. Yoo, J., Sohn, Y.S., and Do, Y., J. Inorg. Biochem.,
1999, vol. 73, no. 3, p. 187. doi 10.1016/S0162-0134
(99)00016-1
9. Majouga, A.G., Zvereva, M.I., Rubtsova, M.P.,
Skvortsov, D.A., Mironov, A.V., Azhibek, D.M.,
Krasnovskaya, O.O., Gerasimov, V.M., Udina, A.V., Vorozh-
tsov, N.I., Beloglazkina, E.K., Agron, L., Mikhina, L.V.,
18. Glushko, V.N. and Sadovskaya, N.Yu., RU Patent
no. 2661871, 2018.
19. Mossman, T., J. Immunol. Meth., 1983, vol. 65, nos. 1–2,
p. 55. doi 10.1016/0022-1759(83)90303-4
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 3 2019