ISSN 1993-6842 (on-line); ISSN 0233-7657 (print)

Biopolymers and Cell. 2020. Vol. 36. N 1. P 75–84

doi: http://dx.doi.org/10.7124/bc.000A22

UDC: 547.789.1+547.722

Synthesis and anticancer properties of N-(5-R-benzyl-1,3-thiazol-

2-yl)-2,5-dimethyl-3-furamides
Y. E. Matiichuk1, YV. Ostapiuk2, TI. Chaban1, VV. Ogurtsov1, VS. Matiychuk2
1 Danylo Halytsky Lviv National Medical University
69, Pekarska Str., Lviv, Ukraine, 79010
2 Ivan Franko National University of Lviv

4, Hrushevskoho Str., Lviv, Ukraine, 79005

matichyk@mail.lviv.ua

Aim. Study of the synthesis and anticancer activity of a series of N-(5-R-benzyl-1,3-thiazol-

2-yl)-2,5-dimethyl-3-furamides. Methods. Organic synthesis, analytical and spectral methods,
pharmacological screening. Results. N-(5-R-benzyl-1,3-thiazol-2-yl)-2,5-dimethyl-3-furamides
7a-g have been prepared in good yields by the reaction of 2-amino-5-(R-benzyl)thiazoles with
2,5-dimethyl-3-furoylchloride. Their structure was confirmed by 1H NMR spectroscopy and
microanalyses. The synthesized compounds have been evaluated for their anticancer activity
against 60 cancer lines in the concentration of 10 µM. The human tumour cell lines were
derived from nine different cancer types: leukemia, melanoma, lung, colon, CNS, ovarian,
renal, prostate, and breast cancers. It was found that compounds 7d,e,g exhibit a high activity
with GP = 29.05–35.02 % whereas 7a-c,f – moderate activity with GP = 60.31–67.36 %. The
most active compound 7g showed a high inhibition activity (GI50<10 µM) against 54 of 58
human tumor cell lines with average GI50 values of 4.22 µM and the colon cancer subpanel
demonstrated the highest sensitivity with [a] mean GI50 value of 2.53 µM. The most sensitive
line was T-47D (BreastCancer, GI50 = 0.088 µM). [The] MG-MID values for the most active
compound 7g are less compared with those for 5-fluorouracil, curcumin and cisplatin when
testing in the same manner. Conclusions. A series of new N-(5-R-benzyl-1,3-thiazol-2-yl)-2,5-
dimethyl-3-furamides were prepared. The compounds with high anticancer activity have been
identified.
K e y w o r d s: organic synthesis, arylation, acylation, 2-amino-5-arylmetylthiazole, anticancer
activity.

Introduction

The diazonim salts are very important as star­ vious works we have developed [the] methods
ting materials in organic synthesis. In our pre- of synthesis of furane [1,2], thiophene [3],

© 2020 YE. Matiichuk et al.; Published by the Institute of Molecular Biology and Genetics, NAS of Ukraine on behalf of Bio-
polymers and Cell. This is an Open Access article distributed under the terms of the Creative Commons Attribution License
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provided the original work is properly cited

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Y. E. Matiichuk, YV. Ostapiuk, TI. Chaban
Y. E. Matiichuk, YV. Ostapiuk, TI. Chaban et al.

pyrazole [4], thiazole[5-7], triazole [8] deriva- Melting points were determinated in open cap-
tives based on using diazonium salt as starting illary tubes and are uncorrected. The purity
reagents. The condensed compounds were also of the compounds was checked by thin-layer
prepared [9-11]. The advantage of the pro- chromatography performed with Merck Silica
posed method is that the synthesis of arene- Gel 60 F254 aluminum sheets.
diazonium salts from low-cost aromatic amines 5-R-benzylthiazol-2-ylamines 5a-g were
abundantly available in the market is very prepared according [to the] procedure de-
simple. It means that the variety of different scribed in [12].
substitutes in organic molecules can be intro-
duced, which is very important for the pur- N-(5-R-benzyl-1,3-thiazol-2-yl)-2,5-di-
poses of medical chemistry. One of the hetero- methylfuran-3-carboxamides(7a-g)
cyclic core prepared by this strategy was General procedure. To a solution of 0.01 mol
2-aminothiazole [5-7, 12], a privileged struc- of 2-aminothiazole 5a-g and 1 ml of triethyl-
ture in medical chemistry[13-16]. amine in 30 ml of anhydrous dioxane we ad­ded
The present work is devoted to the synthe- under stirring 1.59g (0.01 mol) of 2,5-dime­
sis and evaluation of anticancer activity [of] thyl-3-furoyl chloride 6. The mixture was left
N-(5-R-benzyl-1,3-thiazol-2-yl)-2,5-dimethyl- for 0.5 h and diluted with water, and the pre-
3-furamides using diazonium salts as a starting cipitate was filtered off, washed with water,
material. Noteworthy, N-1,3-thiazol-2-yl fu- and recrystallized from mixture alcohol –
ramides display biological activity of different DMF.
kind such as antivarial [17] and antibacterial N-(5-benzyl-1,3-thiazol-2-yl)-2,5-
[18], they are effective against both replicative dimethylfuran-3-carboxamide (7a).
and latent mycobacterium tuberculosis [19, Yield80 %, m.p. 157-158 °C. 1HNMR (400
20], malaria parasites [21], as well as the li- MHz, [D6]DMSO): δ = 11.90 (s, 1H, NH),
gands of adenosine receptors [22], allosteric 7.38–7.25 (m, 5H, C6H4, thiazole), 7.22 (t, J
glucokinase activators [23]and the inhibitors = 7.0 Hz, 1H, C6H4), 6.81 (s, 1H, furane), 4.08
of the Src family kinase p56Lck [24]. The (s, 2H, CH2), 2.49 (s, 3H, CH3), 2.22 (s, 3H,
anticancer properties of N-1,3-thiazol-2-yl fu- CH3). Anal. Calcd. for C17H16N2O2S: C, 65.36;
ramides were also reported [25–28]. H, 5.16; N, 8.97. Found: C, 65.22; H, 5.09;
Considering the above, the synthesis of N-(1,3- N, 8.88.
thiazol-2-yl)-2,5-dimethyl-3-furamides and the 2,5-Dimethyl-N-[5-(3-methylbenzyl)-1,3-
investigation of their biological properties are thiazol-2-yl]furan-3-carboxamide (7b).
[an] actual task. Yield76 %, m.p. 116-117 °C. 1HNMR
(400 MHz, [D6]DMSO): δ = 11.90 (s, 1H,
Materials and Methods NH), 7.27 (s, 1H, thiazole), 7.19 (t, J = 7.4 Hz,
All starting materials were purchased from 1H, C6H4), 7.12–6.99 (m, 3H, C6H4), 6.81 (s,
Merck and used without purification. NMR 1H, furane), 4.03 (s, 2H, CH2), 2.49 (s, 3H,
spectra were determined with Varian Mercury CH3), 2.27 (s, 3H, CH3), 2.22 (s, 3H, CH3).
400 (400 MHz) spectrometer, in DMSO-d6. Anal. Calcd. for C18H18N2O2S: C, 66.23; H,

76
 Synthesis and anticancer properties of N-(5-R-benzyl-1,3-thiazol-2-yl)-2,5-dimethyl-3-furamides

5.56; N, 8.58. Found: C, 66.06; H, 5.49; 8.8 Hz, 2H, C6H4), 6.81 (s, 1H, furane), 4.08
N, 8.41. (s, 2H, CH2), 2.49 (s, 3H, CH3), 2.22 (s, 3H,
2,5-Dimethyl-N-[5-(4-methylbenzyl)-1,3- CH3). Anal. Calcd for C17H15FN2O2S: C,
thiazol-2-yl]furan-3-carboxamide (7c). Yield 61.80; H, 4.58; N, 8.48. Found: C, 61.63; H,
84 %, m.p. 155-156 °C. 1HNMR (400 MHz, 4.51; N, 8.37.
[D6]DMSO): δ = 11.89 (s, 1H, NH), 7.25 (s, N-[5-(4-Chlorobenzyl)-1,3-thiazol-2-yl]-
1H, thiazole), 7.15 (d, J = 7.9 Hz, 2H, C6H4), 2,5-dimethylfuran-3-carboxamide (7g).Yield
7.11 (d, J = 7.9 Hz, 2H, C6H4), 6.80 (s, 1H, 93 %, m.p. 140-141°C. 1H NMR (400 MHz,
furane), 4.02 (s, 2H, CH2), 2.49 (s, 3H, CH3), [D6]DMSO): δ = 11.90 (s, 1H, NH)7.35 д (2H,
2.26 (s, 3H, CH3), 2.22 (s, 3H, CH3). Anal. J = 8.3 Гц, ClС6Н4), 7.30-7.25 м (3H, ClС6Н4
Calcd. for C18H18N2O2S: C, 66.23; H, 5.56; N, +thiazole),6.81 (s, 1H, furane) 4.94 с (2H,
8.58. Found: C, 66.11; H, 5.48; N, 8.47. СН2), 2.49 (s, 3H, CH3), 2.22 (s, 3H, CH3).
N-[5-(4-Ethylbenzyl)-1,3-thiazol-2-yl]-2,5- Anal. Calcd for C17H15FN2O2S: C, 61.73; H,
dimethylfuran-3-carboxamide (7d). 4.57; N, 8.47. Found: C, 61.60; H, 4.53; N,
Yield74 %, m.p. 123-124 °C. HNMR 1 8.35.
(400 MHz, [D6]DMSO): δ = 11.89 (s, 1H,
NH), 7.26 (s, 1H, thiazole), 7.17 (d, J = 8.1 Hz, Results and Discussion
2H, C6H4), 7.14 (d, J = 8.2 Hz, 2H, C6H4), 6.81 A series of new N-(5-R-benzyl-1,3-thiazol-2-
(s, 1H, furane), 4.03 (s, 2H, CH2), 2.56 (q, J = yl)-2,5-dimethyl-3-furamides were prepared
7.6 Hz, 2H, CH2), 2.49 (s, 3H, CH3), 2.22 (s, according to the scheme. The diazonium salts
3H, CH3), 1.15 (t, J = 7.6 Hz, 3H, CH3) Anal. were used as starting material. They react with
Calcd. for C19H20N2O2S: C, 67.03; H, 5.92; N, acroleine under the Meerwein reaction condi-
8.23. Found: C, 66.88; H, 5.80; N, 8.11. tion [29] to form 3-aryl-2-chloropropanales
N-[5-(4-Methoxybenzyl)-1,3-thiazol-2-yl]- [12]. These aldehydes were converted into
2,5-dimethylfuran-3-carboxamide (7e):Yield 5-R-benzyl-thiazol-2-ylamines with high
88 %, m.p. 155-156 °C. 1H NMR (400 MHz, yields according to the previously reported
[D6]DMSO): δ = 11.88 (s, 1H, NH), 7.24 (s, synthetic protocols [12]. The acylation of
1H, thiazole), 7.18 (d, J = 8.5 Hz, 2H, C6H4), 5-(R-benzyl)-1,3-thiazole-2-amines was car-
6.87 (d, J = 8.6 Hz, 2H, C6H4), 6.80 (s, 1H, ried out by the classical method using 2,5-di-
furane), 4.00 (s, 2H, CH2), 3.72 (s, 3H, OCH3), methyl-3-furoyl chloride. The obtained amides
2.49 (s, 3H, CH3), 2.22 (s, 3H, CH3). Anal. 7a-g are high-melted substances of white or
Calcd. for C18H18N2O3S: C, 63.14; H, 5.30; N, grey colour, poorly soluble in non-polar sol-
8.18. Found: C, 63.01; H, 5.22; N, 8.19. vents, good in DMSO and DMF.
N-[5-(4-Fluorobenzyl)-1,3-thiazol-2-yl]- The structure of synthesized compounds
2,5-dimethylfuran-3-carboxamide (7f). was confirmed by 1H NMR and microanalyses.
Yield91 %, m.p. 146-147 °C.1HNMR In [the] 1H NMR spectra, the signals for the
(400 MHz, [D6]DMSO): δ = 11.91 (s, 1H, protons of all the structural units were ob-
NH), 7.31 (dd, JHH = 8.1, JHF =5.7 Hz, 2H, served in their characteristic ranges. The pro-
C6H4), 7.27 (s, 1H, thiazole), 7.13 (t, J = tons of thiazole and furan rings were recorded

77
Y. E. Matiichuk, YV. Ostapiuk, TI. Chaban et al.

S
N
O H2N NH2 NH2
N2Cl O 4 S
2
R R
Cl
3a-g R
O 5a-g
1a-g

N Cl
O
R N
6
O
O
O
7a-g

1,3,5,7 R = H(a), 3-CH3(b), 4-CH3(c), 4-C2H5(d), 4-CH3O(e), 4-F(f), 4-Cl(g)

Scheme. Synthesis of N-(5-R-benzyl-1,3-thiazol-2-yl)-2,5-dimethyl-3-furamides 7a-g.

as singlet at δ 7.24–7.27 ppm and 6.80– Results for each tested compound were re-
6.81ppm respectively. H–N amide protons ported as the percent of growth of the treated
appeared as a singlet at δ11.88–11.91 ppm and cells when compared to the untreated control
methylene groups at 4.00–4.08 ppm. Two oth- cells. The percentage growth was evaluated
er singlets at δ 2.49 and 2.22 ppm indicated spectrophotometrically versus controls not
methyl groups of furan rings. treated with test agents.
Anticancer activity. The synthesized com- The screening results are shown in Table 1.
pounds were selected by the National Cancer The synthesized compounds display different
Institute (NCI) Developmental Therapeutic levels of activity in the in vitro screening on
Program (www.dtp.nci.nih.gov) for the in vitro the tested cell lines. Compounds 7d,e,g showed
cell line screening. The primary anticancer [a] high activity with GP = 29.05–35.02 %
assay was performed at approximately sixty whereas 7a-c,f – [a] moderate [activity] with
human tumor cell lines panel derived from GP = 60.31–67.36 %. Compouds 7d,e were
nine neoplastic diseases, in accordance with very sensitive to the cell lines MDA-MB-435
the protocol of the Drug Evaluation Branch, (Melanoma), HL-60(TB) (Leukemia), SNB-75
National Cancer Institute, Bethesda [30-33]. (CNS Cancer) and compounds 7g – to MDA-
The tested compounds were added to the cul- MB-435 (Melanoma), UACC-62 (Melanoma).
ture at a single concentration (10-5M) and the In all mentioned cases the cytotoxic effect was
cultures were incubated for 48 h. Determination observed. Noteworthy also, compounds 7a-c
of the endpoint was made with a protein bind- stimulate the activity of COLO 205 (Colon
ing dye, sulforhodamine B (SRB). [The] Cancer) cell line with GP = 113.99–115.05 %.

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 Synthesis and anticancer properties of N-(5-R-benzyl-1,3-thiazol-2-yl)-2,5-dimethyl-3-furamides

Table 1. Cytotoxic activity of the tested compounds in the concentration 10−5 M against 60 cancer cell
lines
Test compounds Average growth, % Range of growth, % Most sensitive cell line (cancer line/type) GP, %
7a 65.63 19.92–113.99 KM12 (Colon Cancer) 19.92
NCI-H460 (Non-Small Cell Lung Cancer) 24.52
UACC-62 (Melanoma) 24.89
7b 63.22 20.37–115.05 SF-295 (CNS Cancer) 20.37
KM12 (Colon Cancer) 21.59
NCI-H460 (Non-Small Cell Lung Cancer) 21.65
CAKI-1 (Renal Cancer) 26.52
MCF7 (Breast Cancer) 28.62
7c 67.36 4.22–115.04 MDA-MB-435 (Melanoma) 4.22
K-562 (Leukemia) 29.51
7d 35.02 -21.46 –66.34 MDA-MB-435 (Melanoma) – 21.46
HL-60(TB) (Leukemia) – 21.31
SNB-75 (CNS Cancer) – 4.36
A498 (Renal Cancer) 8.18
MDA-MB-468 (Breast Cancer) 9.50
HT29 (Colon Cancer) 10.83
7e 35.02 -9.34 –70.68 HL-60(TB) (Leukemia) – 9.34
SNB-75 (CNS Cancer) – 8.41
MDA-MB-435 (Melanoma)-0.62
K-562 (Leukemia) 11.41
HT29 (Colon Cancer) 13.61
SR (Leukemia) 14.05
7f 60.31 17.47–112.78 KM12 (Colon Cancer) 17.47
SF-295 (CNS Cancer) 17.79
UACC-62 (Melanoma) 20.18
NCI-H460 (Non-Small Cell Lung Cancer) 21.75
MCF7 (Breast Cancer) 26.90
CAKI-1 (Renal Cancer) 27.69
7g 29.05 -6.27 –68.99 MDA-MB-435 (Melanoma)-6.27
UACC-62 (Melanoma) – 0.02
SR (Leukemia) 1.38
NCI-H460 (Non-Small Cell Lung Cancer) 7.63
K-562 (Leukemia) 8.25
MDA-MB-468 (Breast Cancer) 9.96

Finally, compound 7g was selected for an tometrically versus controls not treated with
advanced assay against a panel of approxi- the test agents after 48-h exposure using the
mately sixty tumor cell lines at 10-fold dilu- SRB protein assay to estimate the cell viabil-
tions of five concentrations (100 µM, 10 µM, ity or growth. The dose–response parameters
1.0 µM, 0.1 µM and 0.01 µM) (Table 2). The were calculated for each cell line: GI50 – mo-
percentage growth was evaluated spectropho- lar concentration of the compound leading to

79
Y. E. Matiichuk, YV. Ostapiuk, TI. Chaban et al.

the 50 % inhibition of net cell growth; TGI – cell lines were included with the highest con-
molar concentration of the compound leading centration tested.
to the total inhibition; and LC50– molar con- The most active compound 7g showed [a]
centration of the compounds leading to [the] high inhibition activity (GI50<10 µM) against
50 % net cell death. Furthermore, the mean 54 of 58 human tumor cell lines with [the]
graph midpoints (MG_MID) were calculated average GI50 values of 4.22 µM and the colon
for GI50, giving an average activity parameter cancer subpanel demonstrated the highest sen-
over all cell lines for the tested compound. For sitivity with [the] mean GI50 value of 2.53 µM
the calculation of MG_MID, the insensitive (Table 2). The most sensitive line was T-47D

Table 2. Influence of compound 7g on the growth of tumor cell lines

Disease Cell line GI50, µM Disease Cell line GI50, µM
Leukemia CCRF-CEM 5.84 Melanoma LOX IMVI 3.31
HL-60(TB) 3.03 MALME-3M 6.12
K-562 1.31 M14 2.83
MOLT-4 3.18 MDA-MB-435 1.58
RPMI-8226 4.97 SK-MEL-2 1.70
SR 0.657 SK-MEL-28 6.77
Non-Small Cell A549/ATCC 1.22 SK-MEL-5 0.398
Lung Cancer EKVX 4.15 UACC-257 5.01
HOP-62 4.63 UACC-62 0.481
HOP-92 4.83 Ovarian Cancer IGROV1 7.82
NCI-H226 21.8 OVCAR-3 3.76
NCI-H23 3.87 OVCAR-4 1.02
NCI-H322M 11.9 OVCAR-5 -
NCI-H460 0.432 OVCAR-8 5.75
NCI-H522 2.64 NCI/ADR-RES 2.21
Colon Cancer COLO 205 4.90 SK-OV-3 12.1
HCC-2998 0.740 Renal Cancer 786-0 2.42
HCT-116 3.54 A498 2.96
HCT-15 0.728 ACHN -
HT29 3.64 CAKI-1 0.798
KM12 0.893 RXF 393 4.88
SW-620 3.24 SN12C 5.07
CNS Cancer SF-268 3.73 TK-10 9.80
SF-295 0.589 UO-31 1.93
SF-539 3.85 Breast Cancer MCF7 0.659
SNB-19 9.37 MDA-MB- 1.51
SNB-75 12.6 231/ATCC
U251 3.58 HS 578T 12.8
Prostate Cancer PC-3 5.92 BT-549 3.70
DU-145 3.21 T-47D 0.088
MDA-MB-468 1.70

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 Synthesis and anticancer properties of N-(5-R-benzyl-1,3-thiazol-2-yl)-2,5-dimethyl-3-furamides

(Breast Cancer, GI50 = 0.088 µM). [The] active compound 7g does not demonstrate any
Values of TGI and LC50 were above the selectivity toward all tested cell lines (Table 3).
100 µM except [the] data of TGI for Non- Table 4 demonstrates that the tested com-
Small Cell Lung Cancer cell lines HOP- pound 7g is effective against all of the cell
92(TGI = 62.5µM), CNS Cancer cell lines lines, as it is shown by the full panel mean-
SF-295 (TGI = 40.0µM) and SNB-75 (TGI = graph. MG-MID (µM) values for 7g are less
90.1µM), Melanoma cell lines MDA-MB-435 than those for 5-fluorouracyl, curcumin and
(TGI = 5.10 µM), SK-MEL-5(TGI = 31.3µM) cisplatin when tested in the same manner.
and UACC-62 (TGI = 90.1 µM), Renal Cancer
cell line MDA-MB-468 (TGI = 56.8µM), RXF Conclusions
393(TGI= 63.7 µM) and Breast Cancer cell A series of novel N-(5-R-benzyl-1,3-thiazol-
line MDA-MB-468 (TGI= 8.29µM). 2-yl)-2,5-dimethylfuran-3-carboxamides were
The selectivity index (SI) obtained by divi­ synthesized and their anticancer activity was
ding the full panel MG-MID (μM) of the com- investigated. The compounds with significant
pound 7g by its individual subpanel MG-MID levels of anticancer activity towards the se-
(μM) was considered as a measure of com- lected cancer cell lines have been found and
pound’s selectivity.The value between 3 and 6 may be used for the further optimization.
refers to moderate selectivity. The index SI
greater than 6 indicates a high selectivity to- Acknowledgements
ward the corresponding cell line, whereas the We are grateful to Dr. VL. Narayanan from
compounds meeting neither of the criteria are Drug Synthesis and Chemistry Branch,
rated as non-selective [34]. In this context, the National Cancer Institute, Bethesda, MD,

Table 3. Anticancer selectivity pattern of the most active compound 7g at the GI50 (С, μМ) levels
Subpanel tumor cell lines
Сpd Parameters
L NSCLC ColC CNSC M OV RC PC BC
7g GI50 3.17 6.16 2.53 5.62 3.13 5.44 3.98 4.57 3.41
SI 1.33 0.69 1.67 0.75 1.35 0.78 1.06 0.92 1.24
L – leukemia, NSCLCC – non-small cell lung cancer, ColC – colon cancer, CNSC – CNS cancer, M – melanoma, OV– ovarian
cancer, RC – renal cancer, PC – prostate cancer, BC – breast cancer.

Table 4. Mean growth inhibitory concentration (GI50, µM) of compound 7g in comparison with 5-FU,
Cisplatin and Curcumin
Subpanel tumor cell lines
Сpd L NSCLC ColC CNSC M OV RC PC BC MG-MID
7g 3.17 6.16 2.53 5.62 3.13 5.44 3.98 4.57 3.41 4.22
5-FU 15.1 >100 8.4 72.1 70.6 61.4 45.6 22.7 76.4 52.5
Cisplatin 6.3 9.4 21.0 4.7 8.5 6.3 10.2 5.6 13.3 9.48
Curcumin 3.7 9.2 4.7 5.8 7.1 8.9 10.2 11.2 5.9 7.41

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Y. E. Matiichuk, YV. Ostapiuk, TI. Chaban et al.

Результати. У результаті взаємодії 2-аміно-5-(R-бензил) диметил-3-фурамидов. Методы. Органический синтез,

тіазолів з 2,5-диметил-3-фуроїлхлоридом було отрима- аналитические и спектральные методы, фармакологи-
но відповідні N-5-R-бензил-1,3-тіазол-2-іл)-2,5- ческий скрининг. Результаты. В результате взаимо-
диметил-3-фураміди 7а-g з хорошими виходами. действия 2-амино-5-(R-бензил)тиазолов с 2,5-диме-
Структуру синтезованих сполук підтверджено 1Н ЯМР тил-3-фуроилхлоридом было получено соответствую-
спектроскопією та мікроаналізом. Протипухлинну ак- щие N-5-R-бензил-1,3-тиазол-2-ил)-2,5-диметил-3-
тивність синтезованих сполук вивчали invitro на 60 фурамиды 7а-g с хорошими выходами. Структуру
лініях ракових клітин у концентрації 10 мкМ. Лінії синтезированных соединений подтверждено методом
пухлинних клітин людини отримували з дев’яти різних спектроскопии1Н ЯМР и микроанализом.
типів раку: лейкемії, меланоми, легенів, товстої кишки, Противоопухолевую активность синтезированных
ЦНС, яєчників, нирки, простати та молочної залози. соединений изучали in vitro на 60 линияхраковых
Встановлено, що сполуки 7d, e, gпроявляють високу клеток в концентрации 10 мкм. Линии опухолевых
активність з GP = 29,05 – 35,02 %, тоді як 7a-c, f–по- клеток человека получали из девяти различных типов
мірну при GP = 60,31–67,36 %. Найактивніша сполука7g рака: лейкемии, меланомы, легких, толстой кишки,
виявила високу інгібуючу активність (GI50<10 мкМ) ЦНС, яичников, почки, простаты и молочной железы.
проти 54 з 58 клітинних ліній пухлин людини із серед- Установлено, что соединения 7d, e, g проявляют вы-
німи значеннями GI50= 4,22 мкМ, а субпанель раку сокую активность с GP = 29,05–35,02  %, тогда как
товстої кишки продемонструвала найвищу активність 7a-c, f– умеренную при GP = 60,31–67,36 %. Для сое-
із середнім значенням GI50= 2,53 мкМ. Найбільш чут- динения7g обнаружено высокую ингибирующую ак-
ливою лінією була Т-47D (Рак молочної залози, GI50 = тивность (GI50<10 мкм) против 54 из 58 клеточных
0,088 мкм). Значення MG-MID для найбільш активної линий опухолей человека со средними значениями
сполуки 7gє меншим, у порівнянні з 5-фторурацилом, GI50= 4,22 мкм, а субпанель рака толстой кишки про-
куркуміном та цисплатином при тестуванні аналогіч- демонстрировала самую высокую активность со сред-
ним чином. Висновки. Отримано ряд нових N-(5-R- ним значением GI50= 2,53 мкМ. Наиболее чувствитель-
бензил-1,3-тіазол-2-іл)-2,5-диметил-3-фурамідів. ной линией была Т-47D (Рак молочной железы, GI50
Виявлено сполуки з високою протираковою активністю. = 0,088 мкМ). Значение MG-MID для наиболее актив-
К л ю ч о в і с л о в а: органічний синтез, арилювання, ного соединения 7g меньше, по сравнению с 5-фтору-
ацилювання, 2-аміно-5-арилметилтіазоли, протипух- рацилом, куркумином и цисплатином при тестирова-
линна активність. нии аналогичным образом. Выводы. Получен ряд
новых N-(5-R-бензил-1,3-тиазол-2-ил)-2,5-диметил-3-
Синтез и противоопухолевые свойства N-(5-R- фурамидов. Обнаруженосоединения с высокой проти-
бензил-1,3-тиазол-2-ил)-2,5-диметил-3- воопухолевойактивностью.
фурамидов К л ю ч е в ы е с л о в а: органический синтез, арили-
Ю. Е. Матийчук, Ю. В. Остапьюк, Т. И. Чабан, рование, ацилирование, 2-амино-5-арилметилтиазолы,
Огурцов В.В., Матийчук В.С. противоопухолевая активность.

Цель. Синтез и исследование противоопухолевой

Received 01.12.2019
активности N-(5-R-бензил-1,3-тиазол-2-ил)-2,5-

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