Synthesis and Antitumor Activity of New 5-Ylidene Derivatives of 3-(Furan-2-ylmethyl)-2-sulfanylidene-1,3-thiazolidin-4-one

Article abstract of DOI:10.1134/S107042802009016X

Abstract: Reactions of 3-(furan-2-ylmethyl)-2-sulfanyidene-1,3-thiazolidin-4-one with aromatic and heterocyclic aldehydes afforded a series of previously unknown 5-[(het)arylmethylidene]-3-(furan-2-ylmethyl)-2-sulfanylidene-1,3-thiazolidin-4-ones. Treatment of 3-(furan-2-ylmethyl)-2-sulfanylidene-1,3-thiazolidin-4-one with thionyl chloride gave in a good yield 3,3′-bis(furan-2-ylmethyl)-2,2′-disulfanylidene-5,5′-bi-1,3-thiazolidinylidene-4,4′-dione which was reduced with zinc in acetic acid to 3,3′-bis(furan-2-ylmethyl)-2,2′-disulfanylidene-5,5′-bi-1,3-thiazolidine-4,4′-dione. The synthesized compounds were screened for antitumor activity.

Full text of DOI:10.1134/S107042802009016X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 9, pp. 1600–1605. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Organicheskoi Khimii, 2020, Vol. 56, No. 9, pp. 1438–1444.
Synthesis and Antitumor Activity of New 5-Ylidene Derivatives
of 3-(Furan-2-ylmethyl)-2-sulfanylidene-1,3-thiazolidin-4-one
V. Ya. Horishnya and V. S. Matiychukb,*
a Danilo Halytsky Lviv National Medical University, Lviv, 79010 Ukraine
b Ivan Franko Lviv National University, Lviv, 79005 Ukraine
*e-mail: v_matiychuk@ukr.net
Received May 31, 2020; revised June 6, 2020; accepted June 11, 2020
Abstract—Reactions of 3-(furan-2-ylmethyl)-2-sulfanyidene-1,3-thiazolidin-4-one with aromatic and hetero-
cyclic aldehydes afforded a series of previously unknown 5-[(het)arylmethylidene]-3-(furan-2-ylmethyl)-2-sul-
fanylidene-1,3-thiazolidin-4-ones. Treatment of 3-(furan-2-ylmethyl)-2-sulfanylidene-1,3-thiazolidin-4-one
with thionyl chloride gave in a good yield 3,3′-bis(furan-2-ylmethyl)-2,2′-disulfanylidene-5,5′-bi-1,3-thiazoli-
dinylidene-4,4′-dione which was reduced with zinc in acetic acid to 3,3′-bis(furan-2-ylmethyl)-2,2′-disul-
fanylidene-5,5′-bi-1,3-thiazolidine-4,4′-dione. The synthesized compounds were screened for antitumor activity.
Keywords: rhodanine, 2-sulfanylidene-1,3-thiazolidin-4-one, furan, thionyl chloride, antitumor activity
DOI: 10.1134/S107042802009016X
Design of highly efficient and low-toxic medicines
and their implementation into medical practice con-
stitute one of the most important problems of organic
and medicinal chemistry. The results of recent studies
of the chemistry and biological activity of rhodanine
(2-sulfanylidene-1,3-thiazolidin-4-one) derivatives
convincingly showed that compounds of this series are
promising as pharmacological agents with a broad
spectrum of activity. Lead compounds exhibiting anti-
microbial, antitubercular, antiviral, antidiabetic, anti-
inflammatory, antitumor, anticonvulsant, and other
activities have been identified among rhodanine deriv-
atives. Therefore, rhodanine fragment is considered
a privileged structure in medicinal chemistry [1–3].
heterocycles [7–20]. It was aimed at synthesizing
5-ylidene derivatives of 3-(furan-2-ylmethyl)-2-sul-
fanylidene-1,3-thiazolidin-4-one and evaluating them
for antitumor activity. Compounds exhibiting valuable
chemotherapeutic properties such as antiviral [21–23],
antifungal [24], trypanocidal [25, 26], and antitumor
activities [27–29] have already been found among
this series.
The target 5-ylidene-3-(furan-2-ylmethyl)-2-sul-
fanylidene-1,3-thiazolidin-4-ones 4a–4k were synthe-
sized by reacting 3-(furan-2-ylmethyl)-2-sulfanylidene-
1,3-thiazolidin-4-one (2) with aromatic and hetero-
cyclic aldehydes 3a–3k (Scheme 1) in boiling acetic
acid in the presence of anhydrous sodium acetate.
Initial rhodanine 2 was prepared by the dithiocarbamate
method (see Experimental). The structure of 4a–4k
was confirmed by 1H NMR spectroscopy. For example,
the 3-CH2 methylene protons resonated in their
1H NMR spectra at δ 5.19–5.26 ppm, and the C5=CH
signal was located at δ 7.67–8.19 ppm, indicating
Z configuration of the exocyclic double bond.
On the other hand, furan compounds have found
applications in various fields of chemistry and technol-
ogy, in particular in pharmacy, due to their unique
physicochemical, chemical, and biological properties
[4–6]. First of all, a broad range of biological activity
of natural and synthetic furan compounds, as well as of
its fused derivatives (benzofuran, naphthofurans,
anthrafurans, etc.), should be noted. In view of the
above stated, there is great interest in the use of furan
heterocycle as an important building block in the
design of medicines.
We also found that treatment of 3-(furan-2-yl-
methyl)-2-sulfanylidene-1,3-thiazolidin-4-one (2) with
thionyl chloride leads to is oxidation with the formation
of 3,3′-bis(furan-2-ylmethyl)-2,2′-disulfanylidene-5,5′-
bi-1,3-thiazolidinylidene-4,4′-dione (5). The latter was
readily reduced to 3,3′-bis(furan-2-ylmethyl)-2,2′-di-
The present study continues our previous works
related to the design of biologically active nitrogen
1600

SYNTHESIS AND ANTITUMOR ACTIVITY OF NEW 5-YLIDENE DERIVATIVES
1601
Scheme 1.
O
S
O
S
(1) CS2, NaOH
(2) ClCH2COOH
O
O
RCHO (3a–3k)
N
N
NH2
O
R
S
S
1
2
4a–4k
HO
MeO
MeO
R = Ph (a),
(b),
(c),
(d),
(e),
(f),
Me
N
H
N
HO
N
N
Me
O
O
O
O
O
O
O
(g),
(h),
(i),
(j),
(k).
N
Cl
O
N
Cl
N
H
O
O
N
H
O
sulfanylidene-5,5′-bi-1,3-thiazolidine-4,4′-dione (6) by
the action of zinc in acetic acid (Scheme 2).
derivatives 4e–4j and 3-(furan-2-yl)prop-2-en-1-
ylidene derivative 4k showed a low activity against
most cancer cell lines tested, but selective sensitivity of
CHB-75 CNS and K-562 leukemia cell lines to these
compounds was observed. Compound 5 showed
a moderate activity against MCF7 breast cancer and
SR leukemia cell lines.
Compounds 4a–4k and 5 were evaluated for their in
vitro antitumor activity against 60 human cancer cell
lines by highly efficient biological screening according
to the International Scientific Program of the US
National Institutes of Health (DTP, Developmental
Therapeutic Program), National Cancer Institute
(Bethesda, Maryland, USA) [30–33]. The tested cell
lines cover almost the entire spectrum of human
malignant tumors, including leukemia, non-small-cell
lung carcinoma, melanoma, and CNS, breast, prostate,
renal, and epithelial colon cancers. Compounds 4a–4k
and 5 were tested at a concentration of 10–5 M, and
their activity was evaluated as cancer cell growth
percentage (% GP) relative to control [30–33]. The
results are collected in Table 1.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Varian
Mercury VX-400 spectrometer at 400 MHz using
DMSO-d6 as solvent and tetramethylsilane as internal
standard.
3-(Furan-2-ylmethyl)-2-sulfanylidene-1,3-thia-
zolidin-4-one. A round-bottom flask equipped with
a reflux condenser was charged with 9.7 g (0.1 mol) of
(furan-2-yl)methanamine and a cold solution of 5.6 g
(0.1 mol) of potassium hydroxide in 30 mL of water.
Carbon disulfide, 8.4 g (0.11 mol), was added dropwise
with stirring over a period of 15 min, the mixture was
stirred for 30 min more, and a solution of 10.4 g
(0.11 mol) of chloroacetic acid and 9.3 g (0.11 mol) of
sodium hydrogen carbonate in 60 mL of water was
added. The mixture was left to stand at room tempera-
ture for 4 days, 50 mL of concentrated aqueous HCl
was added, and the mixture was heated at 95°C for 1 h.
The mixture was cooled, and the precipitate was
Compounds 4a–4k and 5 showed different levels of
antitumor activity. In particular, 5-(3,4-dihydroxyben-
zylidene) derivative 4b generally showed a moderate
antitumor activity, but it appreciably inhibited NST-15
and NST-116 epithelial colon cancer cell lines.
5-(Indol-3-ylmethylidene) derivatives 4c and 4d were
highly active against A-498 (renal cancer), VT-549,
and MDA-MB-468 (breast cancer) cell lines, and com-
pound 4c showed the highest cytotoxicity against
MDA-MB-435 melanoma (GP = –32.74%). Quinoline
Scheme 2.
O
S
O
S
S
S
S
O
O
SOCl2
Zn, AcOH
N
N
2
N
N
O
O
S
S
S
O
O
5
6
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 9 2020

HORISHNY, MATIYCHUK
1602
Table 1. Cytotoxicity of compounds 4b–4k and 5 at a concentration of 10–5 M against most sensitive cancer cell lines
Mitotic activity, % GP
Compound no.
Most sensitive cancer cell lines, % GP
average
range
HCT-15 (Epithelial colon cancer) 20.59
CCRF-CEM (Leukemia) 25.46
HCT-116 (Epithelial colon cancer) 29.57
OVCAR-3 (Melanoma) 30.41
4b
69.33
20.59–109.83
NCI-H522 (Non-small-cell lung carcinoma) 32.26
MDA-MB-435 (Melanoma) –32.74
A498 (Renal cancer) –9.18
CHB-75 (CNS cancer) 1.19
4c
36.17
–32.74 to 89.04
MDA-MB-468 (Breast cancer) 3.03
BT-549 (Breast cancer) 7.24
4d
4e
4f
93.06
88.94
94.72
93.70
92.72
55.04–111.42
50.37–133.54
84.88–115.54
67.65–116.34
57.04–127.71
A498 (Renal cancer) 55.04
CHB-75 (CNS cancer) 50.37
K-562 (Leukemia) 84.88
K-562 (Leukemia) 67.65
HOP-92 (CNS cancer) 57.04
4g
4h
CH12C (Renal cancer) 29.53
CHB-75 (CNS cancer) 32.96
4i
83.53
29.53–131.64
HCT-116 (Epithelial colon cancer) 50.32
4j
93.70
99.19
67.65–106.86
67.55–141.65
K-562 (Leukemia) 67.65
4k
CHB-75 (CNS cancer) 67.55
MCF7 (Breast cancer) 50.13
SR (Leukemia) 54.84
5
92.18
50.13–129.58
5-(3,4-Dihydroxybenzylidene)-3-(furan-2-yl-
methyl)-2-sulfanylidene-1,3-thiazolidin-4-one (4b).
Yield 60%, mp 224–225°C. H NMR spectrum, δ,
filtered off and recrystallized from propan-2-ol. Yield
80%, mp 72–74°C; published data [34]: mp 73–74°C.
1
5-Ylidene 3-(furan-2-ylmethyl)-2-sulfanylidene-
1,3-thiazolidin-4-ones 4a–4k (general procedure).
A round-bottom flask equipped with a reflux condenser
was charged with a solution of 0.64 g (3 mmol) of
compound 2, 3.6 mmol of the corresponding aldehyde
3a–3k, and 0.25 g (3 mmol) of anhydrous sodium
acetate in 5 mL of acetic acid. The mixture was
refluxed for 1.5–2 h and cooled, and the precipitate
was filtered off, washed with acetic acid and water,
dried, and recrystallized from acetic acid or a mixture
of DMF and acetic acid.
ppm: 5.21 s (2H, CH2), 6.40 s (2H, HFu), 6.40 s (2H,
HFu), 6.89 d (1H, HFu, J = 7.9 Hz), 7.05 d (2H, Harom
,
J = 8.1 Hz), 7.59 s (1H, Harom), 7.67 s (1H, CH=).
Found, %: C 53.91; H 3.40; N 4.11. C15H11NO4S2. Cal-
culated, %: C 54.04; H 3.33; N 4.20.
3-(Furan-2-ylmethyl)-5-(5-methoxy-1H-indol-3-
ylmethylidene)-2-sulfanylidene-1,3-thiazolidin-4-
1
one (4c). Yield 60%, mp 227–229°C. H NMR spec-
trum, δ, ppm: 3.83 s (3H, CH3), 5.24 s (2H, CH2),
6.41 d (2H, HFu, J = 3.5 Hz), 6.88 d.d (1H, HFu, J = 8.8,
2.2 Hz), 7.39 d (1H, Harom, J = 8.8 Hz), 7.54 d (1H,
5-Benzylidene-3-(furan-2-ylmethyl)-2-sulfanyli-
H
H
arom, J = 2.1 Hz), 7.59 s (1H, Harom), 7.84 s (1H,
arom), 8.19 s (1H, CH=), 12.30 s (1H, NH). Found, %:
dene-1,3-thiazolidin-4-one (4a). Yield 89%, mp 135–
1
C 58.36; H 3.81; N 7.56. C18H14N2O3S2. Calculat-
ed, %: C 58.47; H 3.89; N 7.49.
136°C. H NMR spectrum, δ, ppm: 5.23 s (2H, CH2),
6.38–6.46 m (2H, HFu), 7.50–7.60 m (4H, Ph, HFu),
7.63–7.67 m (2H, Ph), 7.86 s (1H, CH=). Found, %:
C 59.89; H 3.61; N 4.72. C15H11NO2S2. Calculated, %:
C 59.78; H 3.68; N 4.65.
5-(1,2-Dimethyl-1H-indol-3-ylmethylidene)-3-
(furan-2-ylmethyl)-2-sulfanylidene-1,3-thiazolidin-
4-one (4d). Yield 68%, mp 179–180°C. 1H NMR spec-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 9 2020

SYNTHESIS AND ANTITUMOR ACTIVITY OF NEW 5-YLIDENE DERIVATIVES
1603
trum, δ, ppm: 3.74 s (3H, CH3), 3.82 s (3H, CH3),
5.24 s (2H, CH2), 6.41 s (2H, HFu), 6.92 d (1H, HFu, J =
8.8 Hz), 7.32 s (1H, Harom), 7.48 d (1H, Harom, J =
8.9 Hz), 7.58 s (1H, Harom), 7.76 s (1H, Harom), 8.02 s
(1H, CH=). Found, %: C 62.05; H 4.29; N 7.49.
C19H16N2O2S2. Calculated, %: C 61.93; H 4.38;
N 7.60.
(1H, CH=), 12.12 s (1H, NH). Found, %: C 55.46;
H 2.99; N 6.68. C19H12N2O5S2. Calculated, %:
C 55.33; H 2.93; N 6.79.
8-[(3-(Furan-2-ylmethyl)-4-oxo-2-sulfanylidene-
1,3-thiazolidin-5-ylidenemethyl]-2,3-dihydro-
6H-[1,4]dioxino[2,3-g]quinolin-7-one (4j). Yield
1
99%, mp >270°C. H NMR spectrum, δ, ppm: 4.27 d
3-(Furan-2-ylmethyl)-5-(quinolin-2-ylmethyli-
dene)-2-sulfanylidene-1,3-thiazolidin-4-one (4e).
(2H, CH2, J = 3.5 Hz), 4.35 d (2H, CH2, J = 3.9 Hz),
5.21 s (2H, CH2), 6.39 s (2H, HFu), 6.76 s (1H, Harom),
7.29 s (1H, HFu), 7.58 s (1H, Harom), 7.68 s (1H, Harom),
8.15 s (1H, CH=), 11.92 s (1H, NH). Found, %:
C 56.45; H 3.26; N 6.34. C20H14N2O5S2. Calculat-
ed, %: C 56.33; H 3.31; N 6.57.
1
Yield 70%, mp 198–200°C. H NMR spectrum, δ,
ppm: 5.26 s (2H, CH2), 6.42 s (2H, HFu), 7.59 s (1H,
HFu), 7.65–7.72 m (1H, Harom), 7.81–7.88 m (1H,
Harom), 7.95–8.03 m (3H, CH=, Harom), 8.16 d (1H,
Harom, J = 8.6 Hz), 8.49 d (1H, Harom, J = 7.0 Hz).
Found, %: C 61.45; H 3.36; N 7.86. C18H12N2O2S2.
Calculated, %: C 61.34; H 3.43; N 7.95.
3-(Furan-2-ylmethyl)-5-[3-(furan-2-yl)prop-2-
en-1-ylidene]-2-sulfanylidene-1,3-thiazolidin-4-one
1
(4k). Yield 84%, mp 178–179°C. H NMR spectrum,
3-(Furan-2-ylmethyl)-5-(6-methoxyquinolin-2-
ylmethylidene)-2-sulfanylidene-1,3-thiazolidin-4-
δ, ppm: 5.19 s (2H, CH2), 6.39 d (2H, HFu, J = 3.7 Hz),
6.61–6.74 m (2H, HFu), 6.95 d (1H, HFu, J = 2.6 Hz),
7.28 d (1H, CH=, J = 14.9 Hz), 7.52–7.61 m (2H, CH=,
HFu), 7.87 s (1H, CH=). Found, %: C 56.85; H 3.54;
N 4.35. C15H11NO3S2. Calculated, %: C 56.77; H 3.49;
N 4.41.
1
one (4f). Yield 85%, mp 226–227°C. H NMR spec-
trum, δ, ppm: 3.93 s (3H, CH3), 5.26 s (2H, CH2),
6.41 s (2H, HFu), 7.40 d (1H, HFu, J = 2.2 Hz), 7.47 d
(1H, Harom, J = 9.2 Hz), 7.58 s (1H, Harom), 7.89–7.92 m
(3H, CH=, Harom), 8.04 d (1H, Harom, J = 9.2 Hz).
Found, %: C 59.78; H 3.60; N 7.24. C19H14N2O3S2.
Calculated, %: C 59.67; H 3.69; N 7.32.
3,3′-Bis(furan-2-ylmethyl)-2,2′-disulfanylidene-
5,5′-bi-1,3-thiazolidinylidene-4,4′-dione (5). Com-
pound 2, 2.1 g (10 mmol), was dissolved in 5 mL of
anhydrous toluene on heating in a round-bottom flask
equipped with a reflux condenser, 2.4 g (20 mmol) of
thionyl chloride was added, and the mixture was
refluxed for 3 h. The mixture was cooled, and the
precipitate was filtered off, washed with toluene and
petroleum ether, dried, and recrystallized from DMF.
5-(6-Chloro[1,3]dioxolo[4,5-g]quinolin-7-yl-
methylidene)-3-(furan-2-ylmethyl)-2-sulfanylidene-
1,3-thiazolidin-4-one (4g). Yield 90%, mp 220–221°C.
1H NMR spectrum, δ, ppm: 5.25 s (2H, CH2), 6.27 s
(2H, CH2), 6.44 d (2H, HFu, J = 7.8 Hz), 7.34 s (1H,
HFu), 7.60 s (1H, Harom), 7.63 s (1H, Harom), 7.90 s (1H,
CH=), 8.27 s (1H, Harom). Found, %: C 52.79; H 2.51;
N 6.38. C19H11ClN2O4S2. Calculated, %: C 52.96;
H 2.57; N 6.50.
1
Yield 74%, mp 258–260°C. H NMR spectrum, δ,
ppm: 5.23 s (2H, CH2), 6.41 s (2H, HFu), 6.45 d (2H,
HFu, J = 3.1 Hz), 7.59 s (2H, HFu). Found, %: C 45.56;
H 2.31; N 6.58. C16H10N2O4S4. Calculated, %:
C 45.48; H 2.39; N 6.63.
5-(7-Chloro-2,3-dihydro[1,4]dioxino[2,3-g]quin-
olin-8-ylmethylidene)-3-(furan-2-ylmethyl)-2-sul-
fanylidene-1,3-thiazolidin-4-one (4h). Yield 99%,
1
mp 222–223°C. H NMR spectrum, δ, ppm: 4.41 s
3,3′-Bis(furan-2-ylmethyl)-2,2′-disulfanylidene-
5,5′-bi-1,3-thiazolidine-4,4′-dione (6). Compound 5,
0.42 g (1 mmol), was dissolved in a 2:1 mixture of
DMF and acetic acid on heating in a round-bottom
flask equipped with a reflux condenser, 0.4 g of zinc
dust was added with stirring to the hot solution, the
mixture was slowly heated to the boiling point, the
heating bath was removed, and the mixture was stirred
for 10 min. The mixture was filtered, the filtrate was
diluted with 100 mL of water, and the precipitate was
filtered off, washed with water, dried, and recrystallized
first from dilute acetic acid and then from benzene–
petroleum ether. Yield 67%, mp 140°C (decomp.).
(2H, CH2), 4.43 s (2H, CH2), 5.26 s (2H, CH2), 6.44 d
(2H, HFu, J = 7.9 Hz), 7.37 s (1H, HFu), 7.60 s (1H,
Harom), 7.74 s (1H, Harom), 7.93 s (1H, CH=), 8.34 s
(1H, Harom). Found, %: C 54.11; H 2.90; N 6.42.
C20H13ClN2O4S2. Calculated, %: C 53.99; H 2.95;
N 6.30.
7-[3-(Furan-2-ylmethyl)-4-oxo-2-sulfanylidene-
1,3-thiazolidin-5-ylidenemethyl]-5H-[1,3]dioxolo-
[4,5-g]quinolin-6-one (4i). Yield 97%, mp >270°C.
1H NMR spectrum, δ, ppm: 5.21 s (2H, CH2), 6.14 s
(2H, CH2), 6.40 s (2H, HFu), 6.81 s (1H, Harom), 7.25 s
(1H, HFu), 7.57 s (1H, Harom), 7.68 s (1H, Harom), 8.14 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 9 2020

HORISHNY, MATIYCHUK
1604
1H NMR spectrum, δ, ppm: 5.07 d (2H, CH, J =
4.4 Hz), 5.55 s (4H, CH2), 6.36 s (2H, HFu), 6.39 s (2H,
HFu), 7.56 s (2H, HFu). Mass spectrum (ESI-MS):
m/z 446.8 [M + H]+. Found, %: 45.38; H 2.78; N 6.51.
C16H12N2O4S4. Calculated, %: 45.27; H 2.85; N 6.60.
13. Pokhodylo, N.T., Matiychuk, V.S., and Obushak, M.D.,
Tetrahedron, 2009, vol. 65, p. 2678.
https://doi.org/10.1016/j.tet.2009.01.086
14. Pokhodylo, N.T., Matiychuk, V.S., and Obushak, N.D.,
Chem. Heterocycl. Compd., 2009, vol. 45, p. 121.
https://doi.org/10.1007/s10593-009-0238-2
15. Pokhodylo, N.T., Teslenko, Y.O., Matiychuk, V.S., and
Obushak, M.D., Synthesis, 2009, vol. 2009, no. 16,
p. 2741.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
REFERENCES
https://doi.org/10.1055/s-0029-1216875
16. Pokhodylo, N.T., Matiychuk, V.S., and Obushak, N.B.,
Chem. Heterocycl. Compd., 2009, vol. 45, p. 483.
https://doi.org/10.1007/s10593-009-0287-6
17. Pokhodylo, N.T., Matiychuk, V.S., and Obushak, M.D.,
Synthesis, 2009, vol. 2009, no. 8, p. 1297.
1. Tomasić, T. and Masic, L.P., Curr. Med. Chem., 2009,
vol. 16, p. 1596.
https://doi.org/10.2174/092986709788186200
https://doi.org/10.1055/s-0028-1087992
2. Kaminskyy, D., Kryshchyshyn, A., and Lesyk, R., Expert
Opin. Drug Discovery, 2017, vol. 12, p. 1233.
18. Obushak, N.D., Gorak, Yu.I., Matiichuk, V.S., and
Lytvyn, R.Z., Russ. J. Org. Chem., 2008, vol. 44,
p. 1689.
https://doi.org/10.1080/17460441.2017.1388370
3. Kaminskyy, D., Kryshchyshyn, A., and Lesyk, R., Eur. J.
Med. Chem., 2017, vol. 140, p. 542.
https://doi.org/10.1134/S1070428008110213
19. Obushak, M.D., Matiychuk, V.S., and Lytvyn, R.Z.,
Chem. Heterocycl. Compd., 2008, vol. 44, p. 936.
https://doi.org/10.1007/s10593-008-0135-0
20. Chaban, T.I., Ogurtsov, V.V., Matiychuk, V.S.,
Chaban, I.G., Demchuk, I.L., and Nektegayev, I.A., Acta
Chim. Slov., 2019, vol. 66, p. 103.
https://doi.org/10.1016/j.ejmech.2017.09.031
4. Lukevits, E. and Demicheva, L., Chem. Heterocycl.
Compd., 1993, vol. 29, p. 243.
https://doi.org/10.1007/BF00531499
5. Kleemann, A., Engel, J., Kutscher, B., and Reichert, D.,
Pharmaceutical Substances: Syntheses, Patents,
Applications, Stuttgart: Thieme, 2001, 4th ed.
https://doi.org/10.17344/acsi.2018.4570
21. Rawal, R.K., Tripathi, R.K., Katti, S.B., Panne-
couque, C., and De Clercq, E., Med. Chem., 2007, vol. 3,
p. 355.
6. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Moscow: Meditsina, 1998, 12th ed.
https://doi.org/10.2174/157340607781024393
7. Pokhodylo, N.T. and Matiychuk, V.S., J. Heterocycl.
Chem., 2010, vol. 47, p. 415.
22. Rawal, R.K., Prabhakar, Y.S., Katti, S.B., and
De Clercq, E., Bioorg. Med. Chem., 2005, vol. 13,
p. 6771.
https://doi.org/10.1002/jhet.321
8. Tupys, A., Kalembkiewicz, J., Ostapiuk, Y., Matii-
chuk, V., Tymoshuk, O., Woźnicka, E., and
Byczyński, Ł., J. Therm. Anal. Calorim., 2017, vol. 127,
p. 2233.
https://doi.org/10.1016/ j.bmc.2005.07.063
23. Rawal, R.K., Tripathi, R., Kulkarni, S., Paranjape, R.,
Katti, S.B., Pannecouque, C., and De Clercq, E., Chem.
Biol. Drug Des., 2008, vol. 72, p. 147.
https://doi.org/10.1007/s10973-016-5784-0
https://doi.org/10.1111/j.1747-0285.2008.00683.x
9. Zelisko, N., Atamanyuk, D., Ostapiuk, Y., Bryhas, A.,
Matiychuk, V., Gzella, A., and Lesyk, R., Tetrahedron,
2015, vol. 71, p. 9501.
24. Marques, G.H., Kunzler, A., Bareño, V.D.,
Drawanz, B.B., Mastelloto, H.G., Leite, F.R.,
Nascimento, G.G., Nascente, P.S., Siqueira, G.M., and
Cunico, W., Med. Chem., 2014, vol. 10, p. 355.
https://doi.org/10.1016/j.tet.2015.10.019
10. Pokhodylo, N.T., Savka, R.D., Matiichuk, V.S., and
Obushak, N.D., Russ. J. Gen. Chem., 2009, vol. 79,
p. 309.
https://doi.org/10.2174/15734064113099990030
25. Spinks, D., Smith, V., Thompson, S., Robinson, D.A.,
Luksch, T., Smith, A., Torrie, L.S., McElroy, S.,
Stojanovski, L., Norval, S., Collie, I.T., Hallyburton, I.,
Rao, B., Brand, S., Brenk, R., Frearson, J.A.,
Read, K.D., Wyatt, P.G., and Gilbert, I.H.,
ChemMedChem, 2015, vol. 10, p. 1821.
https://doi.org/10.1134/S1070363209020248
11. Matiichuk, V.S., Potopnyk, M.A., and Obushak, N.D.,
Russ. J. Org. Chem., 2008, vol. 44, p. 1352.
https://doi.org/10.1134/S1070428008090182
https://doi.org/10.1002/cmdc.201500301
12. Zubkov, F.I., Ershova, J.D., Zaytsev, V.P.,
Obushak, M.D., Matiychuk, V.S., Sokolova, E.A.,
Khrustalev, V.N., and Varlamov, A.V., Tetrahedron Lett.,
2010, vol. 51, p. 6822.
26. Havrylyuk, D., Zimenkovsky, B., Karpenko, O.,
Grellier, P., and Lesyk, R., Eur. J. Med. Chem., 2014,
vol. 85, p. 245.
https://doi.org/10.1016/j.tetlet.2010.10.046
https://doi.org/10.1016/j.ejmech.2014.07.103
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 9 2020

SYNTHESIS AND ANTITUMOR ACTIVITY OF NEW 5-YLIDENE DERIVATIVES
1605
27. Appalanaidu, K., Kotcherlakota, R., Dadmal, T.L.,
Bollu, V.S., Kumbhare, R.M., and Patra, C.R., Bioorg.
Med. Chem. Lett., 2016, vol. 26, p. 5361.
Mayo, J., and Boyd, M., J. Natl. Cancer Inst., 1991,
vol. 83, p. 757.
https://doi.org/10.1093/jnci/83.11.757
https://doi.org/10.1016/j.bmcl.2016.08.013
31. Boyd, M.R. and Paull, K.D., Drug Dev. Res., 1995,
vol. 34, p. 91.
28. Kaminskyy, D., den Hartog, G.J.M., Wojtyra, M.,
Lelyukh, M., Gzella, A., Bast, A., and Lesyk, R., Eur. J.
Med. Chem., 2016, vol. 112, p. 180.
https://doi.org/10.1016/j.ejmech.2016.02.011
29. Selvam, T.P., Karthick, V., Kumar, P.V., and Ali, M.A.,
Drug Discovery Ther., 2012, vol. 6, p. 198.
https://doi.org/10.1002/ddr.430340203
32. Boyd, M.R., Anticancer Drug Development Guide:
Preclinical Screening, Clinical Trials, and Approval,
Teicher, B.A., Ed., Totowa: Humana Press, 1997, p. 23.
33. Shoemaker, R.H., Nat. Rev. Cancer, 2006, vol. 6, p. 813.
https://doi.org/10.5582/ddt.2012.v6.4.198
https://doi.org/10.1038/nrc1951
30. Monks, A., Scudiero, D., Skehan, P., Shoemaker, R.,
Paull, K., Vistica, D., Hose, C., Langley, J., Cronise, P.,
Vaigro-Wolff, A., Gray-Goodrich, M., Campbell, H.,
34. Krus, K., Masyas, A., and Beletskaya, I.P., Zh. Org.
Khim., 1988, vol. 24, p. 2024.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 9 2020