Оцінка протиракової активності ди- та трифункціональнозаміщених 1,3-тіазолів
Anticancer activity of a series of polyfunctional substituted 1,3-thiazoles has been studied within the international scientific program “NCI-60 Human Tumor Cell Lines Screen”. Screening was performed in vitro on 60 cell lines of lungs, kidneys, CNS, ovaries, prostate, and breast cancer...
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| Дата: | 2020 |
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| Автори: | , , , , |
| Формат: | Стаття |
| Мова: | Англійська |
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V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
2020
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Ukrainica Bioorganica Acta| _version_ | 1871193564023619584 |
|---|---|
| author | Turov, Kostyantyn V. Mitiukhin, Оleg P. Chumachenko, Svitlana A. Zyabrev, Vladimir S. Brovarets, Volodymyr S. |
| author_facet | Turov, Kostyantyn V. Mitiukhin, Оleg P. Chumachenko, Svitlana A. Zyabrev, Vladimir S. Brovarets, Volodymyr S. |
| author_institution_txt_mv | [
{
"author": "Kostyantyn V. Turov",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine"
},
{
"author": "Оleg P. Mitiukhin",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine"
},
{
"author": "Svitlana A. Chumachenko",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine"
},
{
"author": "Vladimir S. Zyabrev",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine"
},
{
"author": "Volodymyr S. Brovarets",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine"
}
] |
| author_sort | Turov, Kostyantyn V. |
| baseUrl_str | https://bioorganica.com.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-19T14:56:52Z |
| description | Anticancer activity of a series of polyfunctional substituted 1,3-thiazoles has been studied within the international scientific program “NCI-60 Human Tumor Cell Lines Screen”. Screening was performed in vitro on 60 cell lines of lungs, kidneys, CNS, ovaries, prostate, and breast cancer, epithelial cancer, leukemia, and melanoma. The most effective compounds were those with a piperazine substituent at C2 of the 1,3-thiazole cycle: 1-(4-((4-methylphenyl)-sulfonyl)-2-phenyl-1,3-thiazol-5-yl)piperazine (average lg GI50 = -5.87, lg TGI = -5.54, lg LC50 = -5.21), 1-(2-(3,5-dimethyl-1H-pyrazol-1-yl)-4-((4-methylpheyl)sulfonyl)-1,3-thiazol-5-yl)piperazine (average lg GI50 = -5.66, lg TGI = -5.26, lg LC50 = -4.83), and 1-(2,4-bis((4-methylphenyl)sulfonyl)-1,3-thiazol-5-yl)piperazine (average lg GI50 = -5.67, lg TGI = -5.21, lg LC5050 = -4.67). |
| doi_str_mv | 10.15407/bioorganica2020.01.002 |
| first_indexed | 2025-07-17T12:19:28Z |
| format | Article |
| fulltext |
ISSN 1814-9758. Ukr. Bioorg. Acta, 2020, Vol. 15, N 1
UDC 547.789+615.277.3
DOI: https://doi.org/10.15407/bioorganica2020.01.002
2
RESEARCH ARTICLE
Anticancer evaluation of di- and trifunctional substituted 1,3-thiazoles
Kostyantyn V. Turov, Оleg P. Mitiukhin, Svitlana A. Chumachenko, Vladimir S. Zyabrev,
Volodymyr S. Brovarets*
V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine
Abstract: Anticancer activity of a series of polyfunctional substituted 1,3-thiazoles has been studied within the international scientific
program “NCI-60 Human Tumor Cell Lines Screen”. Screening was performed in vitro on 60 cell lines of lungs, kidneys, CNS, ovaries,
prostate, and breast cancer, epithelial cancer, leukemia, and melanoma. The most effective compounds were those with a piperazine
substituent at C2 of the 1,3-thiazole cycle: 1-(4-((4-methylphenyl)sulfonyl)-2-phenyl-1,3-thiazol-5-yl)piperazine (average lg GI50 = -5.87,
lg TGI = -5.54, lg LC50 = -5.21), 1-(2-(3,5-dimethyl-1H-pyrazol-1-yl)-4-((4-methylphenyl)sulfonyl)-1,3-thiazol-5-yl)piperazine (average
lg GI50 = -5.66, lg TGI = -5.26, lg LC50 = -4.83), and 1-(2,4-bis((4-methylphenyl)sulfonyl)-1,3-thiazol-5-yl)piperazine (average lg GI50 =
-5.67, lg TGI = -5.21, lg LC50 = -4.67).
Keywords: 1,3-thiazole; anticancer activity; growth inhibitor; cytostatic activity; cytotoxic activity.
Introduction
Derivatives of 1,3-thiazoles play an important role in
basic and applied research. It has been demonstrated that
1,3-thiazoles are widely used for creation of dyes,
insecticides, herbicides, and pharmaceuticals. Di- and tri-
substituted 1,3-thiazole are effective anti-inflammatory,
anthelmintic, antiviral, and bactericidal agents [1-6]. The
nature of the chemical groups in the heterocycle can
significantly affect their pharmacological properties.
Despite of wide range of thiazole libraries, many of
trisubstituted thiazoles stays unavailable due to multistep
and complicated pathways for its synthesis.
The purpose of this work was to synthesize and evaluate
the antitumor activity of di- and tri- substituted 1,3-thiazole.
SNAr reactions were convenient for direct introduction of
substituents into proper positions of heterocycle. Well
known that substitution of halogen atom in C4 or C5
position demands high temperatures and Pd catalysis.
Received:
Revised:
Accepted:
Published online:
20.03.2020
03.04.2020
10.04.2020
30.06.2020
Corresponding author. Tel.: +380-44-573-2596;
e-mail: brovarets@bpci.kiev.ua (V. S. Brovarets)
ORCID: 0000-0001-6668-3412
Present of EWG makes liable of halogen atom in position 5
of thiazole ring. That allows to modify one by introducing
different O, N and substituents. Such reactions pass in mild
conditions and with high level of regioselectivity, that’s
why yields of desired products was pretty fine.
Results and Discussion
Chemistry
Syntheses of compounds 1-23 are presented in
Schemes 1 and 2. 1-R-3-Tosyl-1,4,4-trichloro-2-aza-1,3-
butadienes I and 1-tosyl-2,2-dichloroethenylisothiocyanate
II were used as starting compounds. Imidoyl chlorides I
react with thiourea to give 2-R-4-tosyl-5-chloro-1,3-
thiazoles 1, 10. 5-Chloro-1,3-thiazole 1 reacts with N-, O-
and S-nucleophiles to eliminate the chlorine anion and form
the corresponding 1,3-thiazole derivatives 2-7. Heating of
compound 3 with hydrogen peroxide in acetic acid followed
by the reaction of the obtained product with morpholine or
benzylamine yields 4-aminosubstituted 5-((4-chlorophenyl)
sulfanyl)-2-phenyl-1,3-thiazoles 8, 9.
1-Tosyl-2,2-dichloroethenylisothiocyanate II was used
for the synthesis of trifunctionally substituted 1,3-thiazoles
11-23. Compound II was treated with thiophenols or alkyl
mercaptans in the presence of pyridine. A cyclization took
place to form intermediate 2-aryl(alkyl)sulfanyl-4-tosyl-5-
© Turov K. V. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
Ukrainica Bioorganica Acta
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ISSN 1814-9758. Ukr. Bioorg. Acta, 2020, Vol. 15, N 1
3
N
SXC6H4S
Ts
Ph
4-
4-
HN N O N
O N4 R1R2N =
8 R1R2N =
9 R1 = H, R2 = PhCH2
R=Ph
N
SCl
Ts
R
Cl
Cl
R
Cl
Ts
N
I
N
SMeS
Ts
Ph
N
SPhO
Ts
Ph
N
SClC6H4S
R1R2N
Ph
N
SR1R2N
Ts
Ph
a b
1,10 2,31 R = Ph
10 R = 2-Fur
2 X = Me
3 X = Cl
4,5
6 7
8,9
c
d e
f X = Cl
R = Ph
R = Ph R = Ph
5 R1R2N =
Scheme 1. Synthesis of 4,5-difunctional substituted 1,3-thiazoles 1-10. Reagents and conditions: (a) (H2N)2C=S (excess), MeCN, reflux,
2 h; (b) 4-MeC6H4SH or 4-ClC6H4SH, Et3N, MeCN, reflux, 2 h; (c) morpholine or piperazine (excess), dioxane, 100 °C, 24 h; (d) NaSH
(excess), THF, 60 °C, 3 h; MeI, MeONa, MeOH, 20 °C, 5 h; (e) PhONa, THF, 20 °C, 24 h; (f) H2O2 (excess), CF3CO2H, reflux, 3 h;
morpholine or PhCH2NH2 (excess), dioxane, 100 °C, 24 h.
chloro-1,3-thiazoles, which were oxidized with hydrogen
peroxide to 1,3-thiazoles III containing at position C2 an
arylsulfonyl or an alkylsulfonyl and at position C4 the tosyl
group. Substitution of the chlorine atom at position C5 of
compounds III with 4-chlorothiophenol followed by the
oxidation of the sulfanyl group under the action of
hydrogen peroxide in trifluoroacetic acid yields 1,3-thiazole
derivatives IV with three different sulfonyl groups.
1,3-Thiazoles 11-16 were obtained under the treatment of
compounds IV by N- and O-nucleophiles. The reaction of
1,3-thiazoles IV with dimethylamine, benzylamine, or
ammonia in a molar ratio of 1:2 at 20 °C yields 2-amino-
1,3-thiazole derivatives 11-13 as a result of replacing a
sulfonyl group at position C2. Treatment of thiazoles IV
with the excess of an amine or sodium 4-chlorophenolate,
leads to the substitution of the two arylsulfonyl groups
yielding compounds 14-16. 1,3-Thiazole 17 was obtained
from reagent II, hydrazine hydrate, and acetylacetone. It
gives when heated with morpholine or piperazine, the
corresponding 5-amino-2-pyrazolyl-4-tosyl-1,3-thiazoles
18, 19 and, when treated with sodium hydrogen sulfide
followed by propyl iodide, 1,3- thiazole 20.
5-Piperazino-substituted 1,3-thiazoles 21, 22 were
prepared by the nucleophilic substitution of the chlorine
atom in compounds III for piperazine in boiling ethanol.
1,3-Thiazole 23 was obtained from isothiocyanate II,
methyl mercaptan, piperazine, and hydrochloric acid.
Structures of synthesized compounds shown in Table 1
were confirmed by 1H NMR spectra and elemental analysis.
Biological Evaluation
Anticancer activity of the synthesized compounds was
studied within an international scientific program of the US
National Institutes of Health. The screening was performed
in vitro on 60 cell lines of lungs, kidneys, CNS, ovaries,
prostate, and breast cancer, epithelial cancer, leukemia, and
melanoma at a substance concentration of 10-5 М. Growth
percentage (GP) of cancer cells compared to the control (in
the absence of a chemical substance, 100%) was determined
[7-10]. Synthesized 1,3-thiazole derivatives have been
shown to be active against several types of cancer cells
(Table 1).
For example, 2-phenyl-4-tosyl-5-chloro-1,3-thiazole (1)
considerably inhibits growth of cells of leukemia (K-562,
GP = 30.07% and SR, GP = 13.60%), lung cancer (NCI-
H522, GP = 44.91%), melanoma (M14, GP = 37.06% and
MDA-MB-435, GP = 1.37%), and breast cancer (MDA-
MB-468, GP = 0.73%).
The replacement of the chlorine atom in compound 1
with p-tolylsulfanyl group (compound 2) results in a
significant 70% reduction of the inhibitory activity towards
leukemia and lung cancer cells and in the full extinction of
the activity towards melanoma cells MDA-MB-435
(GP = 106.38%) and M14 (GP = 102.19%).
The substitution of the chlorine atom by methylsulfanyl
group (compound 6) results in a uniform decrease of the
inhibitory activity towards leukemia and lung cancer cells
and does not change melanoma and breast cancer cells
inhibition. The substitution of the chlorine atom in
compound 1 with morpholine (compound 4) as well as
phenoxy group (compound 7) also does not change
leukemia and melanoma cells growth inhibition. In
summary, any replacement of the chlorine atom results in a
decrease of inhibitory activity in relation to parent
compound 1.
1,3-Thiazoles 8, 9 containing the 4-chlorophenylsulfonyl
group at position C5 and a substituted amino group at
position C4 are somewhat more active than compound 4
with the morpholino group at position C5. Thus, 1,3-thiazole
K. V. Turov, О. P. Mitiukhin, S. A. Chumachenko et al.
4
Cl
Cl
C
Ts
N S
II
N
SCl
Ts
SO2R
III
N
SN
Ts
SO2R
HN
R1R2
21,22
N
SClC6H4SO2
Ts
SO2Ar
N
S
Ts
N
N Me
18 R1R2N =
18,19
IV
R1R2
NO
N
SClC6H4SO2
N
NR1R2
NHN
14 R1 = R2 = (CH2)4
14,15
N
SClC6H4SO2
Ts
NR1R2
N
SCl
Ts
N
N Me
17
4-ClC6H4
11-13
11 R1R2 = Me
N
SPrS
Ts
N
N Me
N
SClC6H4SO2
O
OC6H4Cl-4
II
12 R1 = H, R2 = PhCH2
16
13 R1 = R2 = H
20
N
SN
Ts
SO2Me
HN
. HCl
23
a
f
4-
b
4-
d
e
15 R1 = H, R2 = PhCH2
4-
g
h
4-
c
21 R = 4-MeC6H4
22 R = Pr
i
j
Me Me
Me
N
19 R1R2N =
Scheme 2. Synthesis of 2,4,5-trifunctional substituted 1,3-thiazoles 11-23. Reagents and conditions: (a) ArSH or PrSH, Py, benzene,
15 °C, 8 h; H2O2 (excess), AcOH, reflux, 4 h; (b) 4-ClC6H4SH, Et3N, THF, 5 °C, 30 h; H2O2 (excess), CF3CO2H, reflux 4 h; (c) Me2NH or
PhCH2NH2, or NH3, THF, 20 °C, 24 h; (d) piperidine or PhCH2NH2 (excess), THF, 60 °C, 48 h; (e) 4-ClC6H4ONa (excess), THF, 20 °C,
24 h; (f) NH2NH2 H2O (excess), THF, 20 °C, 5 h; Ac2CH2 (excess), AcOH, reflux, 10 h; (g) morpholine or piperazine (excess), BuOH,
reflux, 20 h; (h) NaSH (excess), MeOH, 20-25 °C, 20 h; PrI, MeONa, MeOH, reflux, 3 h; (i) piperazine (excess), EtOH, reflux, 1 h; (j)
MeSH, Py, benzene, 20-25 °C, 5 h; H2O2 (excess), AcOH, reflux, 4 h; piperazine (excess), EtOH, reflux, 2 h; HCl (excess), 4 °C, 24 h.
8 was active against leukemia HL-60(TB) (GI = 49.92%
and K-562 (GP = 72.30%) as well as breast cancer MDA-
MB-468 (GP = 72.05%) cells. Compound 9 showed
appreciable inhibitory activity only against lung cancer cells
NCI-H522 (GI = 59.56%).
1,3-Thiazole 17 which bears a pyrazole ring instead of
the benzene one at C2 showed lower inhibitory activity
compared with that of the parent compound 1. It showed
only minor activity towards breast cancer cells BT-549
(GP = 84.33%). On the other hand, the substitution of the
chlorine atom in compound 17 with the propylsulfanyl
group results in compound 20, which inhibitory activity
towards lung cancer cells HOP-92 is significantly higher
(GP = 20.91%). The activity of compound 20 against the
other cancer types remains at the level of compound 17.
The replacement of the chlorine atom in compound 17 with
the morpholine cycle does not increase the inhibitory
activity. Compound 18 proved to be practically inactive
towards all types of cancer cells.
Entering a furan cycle in position C2 of the 1,3-thiazole
leads to a significant increase in the anticancer activity.
Thus, synthesized 5-chloro-2-(furan-2-yl)-4-tosyl-1,3-
thiazole (10) was active against leukemia (К-562,
GP = 18.83% and SR, GP = 8.28%), lung cancer (NCI-
H522, GP = 18.49%), melanoma (M14, GP = 32.33% and
MDA-BM-435, GP = 4.90%), and breast cancer (MDA-
MB-468, GP = -22.87%).
The most active were 1,3-thiazoles containing a
piperazine ring in position C5. Thus, compound 19 was
active against epithelial cancer cells HCC-2998 (GP =
-88.55%) and НТ29 (GP = -33.93%), almost all melanoma
lines (MALME-3M, GP = -55.98%; M14, GP = -89.83%;
MDA-MB-435, GP = -2,08%; SK-MEL-28, GP = -83.71%;
SK-MEL-5, GP = 80.68%; UACC-257, GP = -79.19%;
UACC-62, GP = 72.05%), and breast cancer as well
(T-47D, GP = -29.33%; MDA-MB-468, GP = -55.79%).
1,3-Thiazole 21 with two tosyl groups and C5 linked
piperazine also showed high anticancer activity (average
GP = -5.77% ). The most effect was observed on leukemia
HL-60 (TB) (GP = -45.35%), lung cancer NCI-H522
(GP = -44.16%) and NCI-H460 (GP = -38.88%), colon
cancer COLO 205 (GP = -32.92%), CNS cancer SF-539
ISSN 1814-9758. Ukr. Bioorg. Acta, 2020, Vol. 15, N 1
5
(GP = -15.93%), melanoma LOX IMVI (GP = -41.57%),
M14 (GP = -49.08%) and MDA-MB-435 (GP = -43.55%),
prostate cancer DU-145 (GP = -35.29%), breast cancer
HS 578T (GP = -21.17%) and MDA-MB-468 (GP =
-21.44%) cells.
Figure 1. Antitumor activity of 5-(piperazin-1-yl)-4-tosyl-1,3-
thiazoles 5, 19, 21-23.
2-Phenyl-5-(piperazin-1-yl)-4-tosyl-1,3-thiazole (5) has
been a prominent anticancer agent. It significantly
decreased the growth of ovarian cancer cells (IGROV-1,
GP = 31.39% and OVCAR, GP = 49.75%), and destroyed,
with the average GP of -70%, almost all cell lines of
leukemia, melanoma, and colon, CNS, kidney, and breast
cancer. The most significant are the data reflecting the
almost complete destruction of the following cell lines:
colon cancer HCC2998 (GP = -96.68%), CNS U251
(GP = -91.74%), melanoma SK-MEL-28 (GP = -97.03%)
and SK-MEL-5 (GP = -98.77%), kidney cancer ТК-10
(GP = -88.46%), breast cancer MCF7 (GP = -84.29%) and
MDA-MB-468 (GP = -84.34%).
Advanced in vitro study of compounds 5, 19, 21 at five
concentrations of the 10-fold dilution (10-4-10-8 М) was also
performed towards 60 human cancer cell lines, the set of
which was identical to that for the pre-screening stage
(Table 2). High antitumor potential of compound 21 has
been confirmed by a significant level of inhibition (average
lg GI50 = -5.67), as well as cytostatic (average lg TGI =
-5.21) and cytotoxic (average lg LC50 = -4.67) effects.
The highest data were found for compound 5: average
lg GI50 = -5.87, lg TGI = -5.54, and lg LC50 = -5.21.
It is of interest that among the 5-piperazino-substituted
1,3-thiazoles 5, 19, 21-23 compounds 22, 23 containing a
C2 linked alkylsulfonyl group exhibit the lowest level of
antitumor activity. This is readily illustrated by Figure 1
with some selected cell lines. The average activity value of
compounds 22 and 23 was 95.48% and 98.61%,
respectively (Table 1).
Conclusions
The study of the antitumor activity of di- and
trifunctionally substituted 1,3-thiazoles towards the NCI 60
human cancer cell lines revealed "leader compounds" –
5-(piperazin-1-yl)-4-tosyl-1,3-thiazoles. Therein, the nature
of the substituent at C2 of the 1,3-thiazole cycle critically
affects the level of activity. Most preferred is the presence
of phenyl, tosyl or 3,5-dimethyl-1H-pyrazol-1-yl substituent
in this position.
Table 1. Mitotic activity of the 1,3-thiazole derivatives towards NCI 60 cell lines at the 10-5 M concentration.
Compd
Structure
Average GP The most sensitive cell lines (GP)
1
85.92
leukemia K-562 (30.07), SR (13.60);
lung cancer NCI-H522 (44.91);
melanoma М-14 (37.06), MDA-MB-435 (1.37);
breast cancer MDA-MB-468 (0.73)
2
97.48
leukemia K-562 (90.20), SR (88.33);
lung cancer NCI-H522 (83.67);
melanoma М-14 (109.28), MDA-MB-435 (119.03);
kidney cancer CAKI-1 (71.89)
4
100.29
leukemia K-562 (103.76), SR (88.33);
lung cancer NCI-H522 (75.91);
melanoma MDA-MB-435 (106.38);
breast cancer T-47D (70.39)
5
-52.89
colon cancer HCC-2998 (-96.68);
melanoma SK-MEL-5 (-98.77);
CNS cancer U251 (-91.74);
breast cancer MDA-MB-468 (-84.34)
K. V. Turov, О. P. Mitiukhin, S. A. Chumachenko et al.
6
Table 1. (Contd.)
Compd
Structure
Average GP The most sensitive cell lines (GP)
6
89.71
leukemia K-562 (58.49), SR (49.84);
lung cancer NCI-H522 (74.11);
melanoma М-14 (94.70), MDA-MB-435 (36.78);
breast cancer MDA-MB-468 (65.56)
7
90.45
leukemia SR (95.44);
lung cancer NCI-H522 (85.13);
melanoma М-14 (101.29), MDA-MB-435 (107.97);
breast cancer T-47D (54.11)
8
94.46
leukemia HL-60(TB) (49.92), SR (92.70);
lung cancer NCI-H522 (83.12);
melanoma М-14 (101.29), MDA-MB-435 (107.63);
breast cancer MDA-MB-468 (72.05)
9
92.98
leukemia K-562 (88.04), SR (77.65);
lung cancer NCI-H522 (59.56);
melanoma М-14 (100.66), MDA-MB-435 (107.82);
breast cancer MDA-MB-468 (96.90)
10
71.98
leukemia K-562 (18.83), SR (8.28);
lung cancer NCI-H522 (18.49);
melanoma М-14 (32.33), MDA-MB-435 (4.90);
breast cancer MDA-MB-468 (-22.87)
11
84.17
leukemia HL-60(TB) (52.69);
lung cancer A549/ATCC (56.18);
melanoma UACC62 (59.80);
breast cancer MDA-MB-468 (66.25)
12
107.47
CNS cancer SNB-75 (64.32);
melanoma UACC-62 (79.75)
13
91.75
leukemia CCRF-CEM (72.45), HL-60(TB) (72.65),
K-562 (73.24), MOLT (64.64);
lung cancer HOP-92 (47.03)
14
100.46
leukemia K-562 (114.19), SR (100.78);
lung cancer NCI-H522 (91.60);
melanoma М-14 (106.27);
breast cancer MDA-MB-468 (94.07);
CNS cancer SNB-75 (73.04)
15
84.40
leukemia HL-60(TB) (81.31), K-562 (85.08);
lung cancer A549/ATCC (44.72), NCI-H522 (49.57);
melanoma М-14 (77.99), MDA-MB-435 (114.47);
breast cancer MDA-MB-231/ATCC (42.35)
ISSN 1814-9758. Ukr. Bioorg. Acta, 2020, Vol. 15, N 1
7
Table 1. (Contd.)
Compd
Structure
Average GP The most sensitive cell lines (GP)
16
98.55
leukemia HL-60(TB) (71.46), K-562 (96.63),
SR (43.24);
lung cancer NCI-H522 (88.25);
melanoma М-14 (99.61), MDA-MB-435 (96.32);
breast cancer MCF7 (76.99)
17
102.42
leukemia K-562 (92.44);
lung cancer NCI-H522 (89.59);
melanoma М-14 (111.85), MDA-MB-435 (107.95);
breast cancer BT-549 (84.33)
18
89.56
leukemia MOLT-4 (81.01), K-562 (81.84);
lung cancer HOP-92 (20.91), NCI-H522 (78.32);
CNS cancer SNB-19 (77.87);
breast cancer MDA-MB-231/АТСС (68.26)
19
23.20
leukemia SR (-8.89);
colon cancer HCC-2998 (-88.55);
melanoma SK-MEL-28 (-83.71);
breast cancer MDA-MB-468 (-55.79)
20
89.56
leukemia MOLT-4 (81.01), K-562 (92.44);
lung cancer HOP-92 (20.91), NCI-H322М (88.60);
CNS cancer SNB-19 (98.94);
breast cancer MDA-MB-468 (117.20)
21
-5.77
leukemia HL-60(TB) (-45.35);
lung cancer NCI-H522 (-44.16);
melanoma М-14 (-49.08);
ovarian cancer OVCAR-3 (-40.27);
prostate cancer DV-145 (-35.29)
22
95.48
leukemia SR (64.37);
colon cancer SW-620 (134.85);
melanoma М-14 (76.23);
ovarian cancer OVCAR-3 (136.53);
breast cancer MDA-MB-468 (66.81)
23
98.61
colon cancer HCC-2998 (-88.55);
CNS cancer SNB-19 (98.94);
renal cancer RXF-393 (115.77);
breast cancer MCF-7 (82.11),
MDA-MB-468 (75.35)
K. V. Turov, О. P. Mitiukhin, S. A. Chumachenko et al.
8
Table 2. Parameter values (lg) of the anticancer activity of compounds 5, 19, 21 against the NCI 60 human cancer cell lines
(five-dose assay).
Cell Line
Compd
5 19 21
GI50 TGI LC50 GI50 TGI LC50 GI50 TGI LC50
Leukemia
CCRF-CEM -5.73 -5.28 -4.23 -5.57 -4.96 -4.21 -5.63 -5.05 -4.35
HL-60(TB) -5.72 -5.43 -5.14 -5.62 -5.35 -5.07 -5.64 -5.32 -5.00
K-562 -6.26 -5.62 -5.11 -5.81 -5.39 -4.91 NT NT NT
MOLT-4 -5.74 -5.39 -5.03 -5.65 -5.31 -4.88 -5.52 -5.23 -4.53
RPMI-8226 NT NT NT NT NT NT -5.94 -5.01 -4.19
SR -5.87 -5.47 -5.08 -5.64 -5.24 -4.49 -5.63 -5.31 -4.38
Non-small cell lung cancer
A549/ATCC -5.74 -5.47 -5.20 -5.44 -4.89 -4.38 -5.64 -5.10 -4.48
EKVX -5.87 -5.52 -5.16 -5.63 -4.90 -4.39 -5.49 -4.91 -4.40
HOP-62 -5.77 -5.51 -5.26 -5.71 -5.39 -5.07 -5.92 -5.39 -4.70
HOP-92 -6.46 -5.79 -5.37 -6.21 -5.50 -4.83 -5.45 -5.12 -4.57
NCI-H226 -5.79 -5.51 -5.23 -5.57 -5.00 -4.38 -5.67 -5.37 -5.06
NCI-H23 -5.84 -5.53 -5.23 -5.29 -4.71 -4.34 -5.63 -5.17 -4.55
NCI-H322M NT NT NT NT NT NT NT NT NT
NCI-H460 -5.79 -5.52 -5.24 -5.74 -5.45 -5.16 -5.64 -5.20 -4.55
NCI-H522 -5.74 -5.46 -5.18 -5.67 -5.39 -5.10 NT NT NT
Colon cancer
COLO 205 -6.68 -6.33 -5.95 -5.78 -5.52 -5.25 -5.78 -5.45 -5.12
HCC-2998 -6.28 5.76 -5.34 -5.81 -5.52 -5.22 -5.59 5.22 -4.66
HCT-116 -5.93 -5.61 -5.29 -5.79 -5.49 -5.18 -5.75 -5.39 -5.04
HCT-15 -5.84 -5.54 -5.24 -5.67 -5.31 -4.86 -5.70 -5.07 -4.47
HT29 -6.12 -5.65 -5.24 -5.82 -5.40 -4.95 -5.56 -4.98 -4.30
KM12 -5.79 -5.51 -5.24 -5.74 -5.48 -5.22 -5.61 -5.18 -4.50
SW-620 -5.82 -5.54 -5.26 -5.77 -5.48 -5.19 -5.79 -5.44 -5.09
CNS cancer
SF-268 -5.80 -5.50 -5.20 -5.48 -4.92 -4.43 -5.58 -5.09 -4.46
SF-295 -5.77 -5.49 -5.21 -5.73 -5.43 -5.14 -5.60 -5.19 -4.59
SF-539 -5.81 -5.53 -5.24 -5.77 -5.46 -5.14 -5.56 -5.25 -4.83
SNB-19 -5.75 -5.36 -4.88 -5.16 -4.68 -4.30 -5.51 -4.95 -4.45
SNB-75 -5.97 -5.62 -5.27 -5.85 -5.39 -4.87 -5.59 -5.09 -4.54
U251 NT NT NT NT NT NT -5.55 -5.01 -4.45
Melanoma
LOX IMVI -5.88 -5.57 -5.26 -5.75 -5.45 -5.15 -5.82 -5.39 -4.86
MALME-3M -5.77 -5.50 -5.22 -5.33 -4.79 -4.36 -5.61 -5.34 -5.06
M14 -5.76 -5.47 -5.19 -5.67 -5.41 -5.16 -5.80 -5.48 -5.15
MDA-MB-435 -5.87 -5.55 -5.24 -5.75 -5.45 -5.16 -6.23 -5.65 -5.17
SK-MEL-2 -5.69 -5.42 -5.15 -5.65 -5.40 -5.15 NT NT NT
SK-MEL-28 -5.81 -5.54 -5.27 -5.76 -5.50 -5.24 -5.74 -5.44 -5.14
SK-MEL-5 -5.82 -5.55 -5.27 -5.78 -5.52 -5.26 -5.84 -5.55 -5.27
UACC-257 -5.80 -5.50 -5.19 -5.77 -5.48 -5.20 -5.79 -5.48 -5.17
UACC-62 -5.80 -5.53 -5.26 -5.77 -5.49 -5.22 -5.79 -5.28 -4.68
Ovarian cancer
IGROV1 -5.75 -5.44 -5.14 -5.74 -5.45 -5.17 -5.60 -5.13 -4.37
OVCAR-3 -5.77 -5.50 -5.23 -5.59 -5.15 -4.59 -5.61 -5.28 -4.83
OVCAR-4 -5.76 -5.46 -5.16 -5.38 -4.81 -4.40 -5.56 -4.92 -4.39
OVCAR-5 -5.80 -5.51 -5.22 -5.50 -4.95 -4.46 -5.44 -5.05 -4.51
OVCAR-8 -5.75 -5.46 -5.17 -5.64 -5.22 -4.47 -5.65 -4.99 -4.35
NCI/ADR-RES -5.81 -5.49 -5.17 -5.50 -4.84 -4.32 -5.55 -4.92 -4.34
SK-OV-3 -5.76 -5.49 -5.23 -5.53 -5.11 -4.57 -5.50 -4.97 -4.43
ISSN 1814-9758. Ukr. Bioorg. Acta, 2020, Vol. 15, N 1
9
Table 2. (Contd.)
Cell Line
Compd
5 19 21
GI50 TGI LC50 GI50 TGI LC50 GI50 TGI LC50
Renal cancer
786-0 -5.79 -5.48 -5.17 -5.66 -5.29 -4.77 -5.65 -5.37 -5.08
A498 -5.00 -5.66 -5.33 -5.91 -5.50 -5.08 -5.74 -5.34 -4.84
ACHN -5.78 -5.50 -5.21 -5.46 -4.92 -4.45 -5.41 -4.91 -4.44
CAKI-1 -5.82 -5.50 -5.18 -5.68 -5.23 -4.65 -5.66 -5.34 -5.03
RXF 393 -5.90 -5.59 -5.29 -5.77 -5.45 -5.12 -5.80 -5.52 -5.24
SN12C -5.80 -5.51 -5.23 -5.63 -5.15 -4.54 -5.57 -4.99 -4.47
TK-10 -5.76 -5.48 -5.20 -5.58 -5.19 -4.66 -5.42 -4.99 -4.46
UO-31 -5.94 -5.61 -5.29 -5.88 -5.54 -5.20 -5.49 -5.00 -4.45
Prostate cancer
PC-3 -5.81 -5.48 -5.15 -5.52 -4.99 -4.46 -5.51 -4.88 -4.41
DU-145 -5.79 -5.52 -5.25 -5.43 -4.88 -4.44 -5.66 -5.28 -4.76
Breast cancer
MCF7 -5.84 -5.55 -5.26 -5.76 -5.43 -5.10 -5.78 -5.21 -4.44
MDA-MB-231/ATCC -5.83 -5.54 -5.25 -5.74 -5.44 -5.13 -5.54 -5.16 -4.62
HS 578T -5.81 -5.45 -5.09 -5.68 -5.24 -4.25 -5.61 -5.14 -4.00
BT-549 -5.78 5.51 5.23 -5.47 -4.91 -4.43 -5.52 5.11 4.57
T-47D -5.80 -5.50 -5.19 -5.76 -5.46 -5.16 -6.29 -5.18 -4.43
MDA-MB-468 -6.56 -6.01 -5.44 -5.92 -5.61 -5.30 -6.43 -5.77 -5.23
Experimental section
Chemistry
1H NMR spectra were obtained on a Bruker Avance
DRX 500 spectrometer. The melting points were estimated
on a Fisher-Johns apparatus. The reaction progress was
monitored by the TLC method on silica gel 60F254 Merck
plates. All reagents and solvents were purchased from
Aldrich and used without additional purification.
5-Substituted 4-[(4-methylphenyl)sulfonyl]-2-phenyl-1,3-
thiazoles 1-4, 6-9 [11], 5-Chloro-2-(furan-2-yl)-4-((4-
methylphenyl)sulfonyl)-1,3-thiazole (10) [12], 2,4-Di-
substituted 5-(4-chlorophenyl)sulfonyl-1,3-thiazoles 11-16
[13], 2-(3,5-Dimethyl-1H-pyrazol-1-yl)-4-((4-methylphe-
nyl)sulfonyl)-1,3-thiazoles 17, 18 [14] were synthesized
following the procedures described in the corresponding
sources cited.
1-(4-((4-Methylphenyl)sulfonyl)-2-phenyl-1,3-thiazol-5-
yl)piperazine (5) was synthesized similarly to compound 4.
Yield 67%, mp 112-113 °C (EtOH). 1H NMR (500 MHz,
CDCl3) δ 2.45 (s, 3H, CH3), 3.20-3.35 (m, 4H, 2CH2), 3.82-
3.94 (m, 4H, 2CH2), 7.33-7.45 (m, 5H, Ar), 7.78 (d, J 7.5
Hz, 2H, Ar), 8.05 (d, J 7.5 Hz, 2H, Ar). Anal. Calcd. for
C20H21N3O2S2: C, 60.12; H, 5.30; N, 10.52; S, 16.05.
Found: C, 59.98; H, 5.15; N, 10.32; S, 15.98.
1-(2-(3,5-Dimethyl-1H-pyrazol-1-yl)-4-((4-methylphe-
nyl)sulfonyl)-1,3-thiazol-5-yl)piperazine (19) was synthesi-
zed similarly to compound 18.
Yield 62%, mp 98-99 °C (EtOH). 1H NMR (500 MHz,
CDCl3) δ 2.17 (s, 3H, CH3), 2.40 (s, 3H, CH3), 2.44 (s, 3H,
CH3), 3.79-3.88 (m, 4H, 2CH2), 4.12-4.23 (m, 4H, 2CH2),
6.00 (s, 1H, CH), 7.38 (d, J 7.9 Hz, 2H, Ar), 7.82 (d, J 7.9
Hz, 2H, Ar). Anal. Calcd. for C19H23N5O2S2: C, 54.65;
H, 5.55; N, 16.77; S, 15.36. Found: C, 54.48; H, 5.49;
N, 16.54; S, 15.12.
2-(3,5-Dimethyl-1H-pyrazol-1-yl)-4-((4-methylphenyl)-
sulfonyl)-5-(propylsulfanyl)-1,3-thiazole (20).
To a suspension of 0.00015 mol of compound 17 in 10
ml of methanol, 0.00075 mol of sodium hydrosulfide was
added. The mixture was stirred for 20 h at 20 °C, the
precipitate was filtered off, and the filtrate was evaporated
in vacuo. To the residue, 5 ml of water followed by 1 ml of
concd hydrochloric acid was added to precipitate a solid,
which was filtered off. To a suspension of this solid in 5 ml
of methanol, 0.00015 mol of sodium methylate followed by
0.0002 mol of propyl bromide was added. The mixture was
refluxed for 3 h then cooled to 20 °C, the precipitate was
filtered off and recrystallized from ethanol. Yield 65%,
mp 142-144 °C (EtOH). Anal. Calcd. for C18H21N3O2S3:
C, 53.04; H, 5.19; N, 10.31; S, 23.60. Found: C, 52.91;
H, 5.00; N, 10.18; S, 23.54.
General procedure for preparation of compounds (21,
22).
To a solution of 0.08 mol of compound II [15] in 150 ml
of benzene cooled to 0 °C, 0.08 mol of 4-methyl-
benzenethiol or propanethiol followed by 0.08 mol of
pyridine was added. The mixture was stirred for 8 h at
15 °C, the solvent was removed in vacuo, the residue was
K. V. Turov, О. P. Mitiukhin, S. A. Chumachenko et al.
10
washed with water, and dissolved in 200 ml of acetic acid.
To this solution, 30 ml of a 30% aqueous hydrogen
peroxide solution was added, the reaction mixture was
boiled for 4 h then cooled to 10 °C. The precipitate was
filtered off and dissolved in 50 ml of ethanol. To this
solution, 0.25 mol of piperazine was added, the reaction
mixture was boiled for 1 h then evaporated in vacuo. To the
residue, 20 ml of water was added to precipitate a solid,
which was filtered off and recrystallized from ethanol.
1-(2,4-Bis((4-methylphenyl)sulfonyl)-1,3-thiazol-5-yl)-
piperazine (21).
Yield 72%, mp 132-133 °C (EtOH). 1H NMR (500 MHz,
CDCl3) δ 2.43 (s, 3H, CH3), 2.47 (s, 3H, CH3), 3.80-3.89
(m, 4H, 2CH2), 4.15-4.30 (m, 4H, 2CH2), 7.29 (d, J 7.6 Hz,
2H, Ar), 7.35 (d, J 7.9 Hz, 2H, Ar), 7.38 (d, J 7.6 Hz, 2H,
Ar), 7.86 (d, J 7.9 Hz, 2H, Ar). Anal. Calcd. for
C21H23N3O4S3: C, 52.70; H, 4.78; N, 8.80; S, 20.14. Found:
C, 52.81; H, 4.85; N, 8.63; S, 20.04.
1-(4-((4-Methylphenyl)sulfonyl)-2-(propylsulfonyl)-1,3-
thiazol-5-yl)piperazine (22).
Yield 68%, mp 131-132 °C (EtOH). 1H NMR (500 MHz,
CDCl3) δ 0.91 (t, J 7.4 Hz, 3H, CH3), 1.55-1.68 (m, 2H,
CH2), 2.45 (s, 3H, CH3), 3.02-3.18 (m, 4H, 2CH2), 3.19-
3.31 (m, 4H, 2CH2), 3.33-3.45 (m, 4H, 2CH2), 7.34 (d, J 7.5
Hz, 2H, Ar), 7.89 (d, J 7.5 Hz, 2H, Ar). Anal. Calcd. for
C17H23N3O4S3: C, 47.53; H, 5.03; N, 9.78; S, 22.39. Found:
C, 47.45; H, 4.93; N, 9.65; S, 22.10.
1-(4-((4-Methylphenyl)sulfonyl)-2-(methylsulfonyl)-1,3-
thiazol-5-yl)piperazine (23).
To a solution of 0.0026 mol of isothiocyanate II [15] and
00078 mol of pyridine in 10 ml of benzene, methanethiol
was passed, obtained by the hydrolysis of 0.012 mol of
S-methyl-isothiouronium sulfate. The mixture was stirred
for 5 h, the precipitate was filtered off, and the filtrate was
evaporated in vacuo. To the residue, 4 ml of acetic acid
followed by 1.5 ml of 30% aqueous hydrogen peroxide
solution was added. The reaction mixture was heated under
reflux for 1.5 h then cooled to room temperature and the
precipitate was separated. To a suspension of this solid in
5 ml of acetonitrile, 0.005 mol of piperazine was added.
The mixture was stirred for 20 h and the precipitate was
filtered off. To the filtrate, 0.5 ml of concd hydrochloric
acid was added, the mixture was kept at 4 °C for 1 day,
and the precipitate was separated. Yield 25%,
mp 245-247 °C (dec.). 1H NMR (500 MHz, DMSO-d6)
δ 2.39 (s, 3H, CH3), 3.28 (s, 4H, 2CH2), 3.36 (s, 3H, CH3),
3.56 (s, 4H, 2CH2), 7.46 (d, J 8.0 Hz, 2H, Ar), 7.86 (d, J 8.1
Hz, 2H, Ar), 9.54 (s, 2H, NH, HCl). Anal. Calcd. for
C15H20ClN3O4S3: C, 41.13; H, 4.60; Cl, 8.09; N, 9.59;
S, 21.96. Found: C, 41.24; H, 4.57; Cl, 8.17; N, 9.65;
S, 21.85.
Biological tests
Anticancer in vitro screening methodology as well as
data interpretation rules is described in details at the NCI
Development Therapeutics Program site [16].
Notes
Acknowledgements. We would like to thank National
Cancer Institute, Bethesda, MD, US for the anticancer
activity investigations and Enamine Ltd. for the material
and technical support.
References
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Reactions of 4-tosyl-2-phenyl-5-chloro-1, 3-thiazole with N-, O-, and
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ISSN 1814-9758. Ukr. Bioorg. Acta, 2020, Vol. 15, N 1
11
Оцінка протиракової активності ди- та трифункціональнозаміщених 1,3-тіазолів
К. В. Туров, О. П. Мітюхін, С. А. Чумаченко, В. С. Зябрєв, В. С. Броварець*
Інститут біоорганічної хімії та нафтохімії ім. В. П. Кухаря НАН України, вул. Мурманська, 1, Київ, 02094,Україна.
Резюме: Cинтезовано ряд ди- та трифункціональнозаміщених 1,3-тіазолів з використанням в якості вихідних сполук 1-R-3-тозил-1,4,4-трихлоро-
2-аза-1,3-бутадієнів або 1-тозил-2,2-дихлороетенілізотіоціанату. Скринінгові дослідження протиракової активності синтезованих сполук
проведено in vitro на 60 лініях ракових клітин людини: лейкемії (лінії CCRF-CEM, HL-60 (TB), K-562, MOLT-4, RPMI-8226, SR), меланоми (лінії
LOX IMVI, MALME-3M, M14, MDA-MB-435, SK-MEL-2, SK-MEL-28, SK-MEL-5 , UACC-257, UACC-62), раку легенів (лінії A549/ATCC, EKVX,
HOP-62, HOP-92, NCI-H226, NCI-H23, NCI-H322M, NCI-H460, NCI-H522), товстої кишки (лінії COLO 205, HCC-2998, HCT-116, HCT-15, HT29,
KM12, SW-620), мозку (лінії SF-268, SF-295, SF-539, SNB-19, SNB-75, U251), яєчників (лінії IGROV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-
8, NCI/ADR-RES, SK-OV-3), нирок (лінії 786-0, A498, ACHN, CAKI-1, RXF 393, SN12C, TK-10, UO-31), простати (лінії PC-3, DU-145) і грудей
(лінії MCF7, MDA-MB-231/ATCC, HS 578T, BT-549, T- 47D, MDA-MB-468) при концентрації 1·10-5 М. В результаті визначено відсоток росту
(GР) клітин ліній раку у порівнянні з контролем (контроль – 100%). Поглиблений in vitro скринінг сполук полягав у вивченні її протипухлинного
ефекту в п`яти концентраціях при 10-кратному розведенні (10-4-10-8 М). У результаті експерименту розраховано 3 дозозалежні параметри (GI50,
TGI, LC50). Серед даних сполук 1-(4-((4-метилфеніл)сульфоніл)-2-феніл-1,3-тіазол-5-іл)піперазин (середні значення lg GI50 = -5.87, lg TGI = -5.54,
lg LC50 = -5.21), 1-(2-(3,5-диметил)-1Н-піразол-1-іл)-4-((4-метилфеніл)сульфоніл)-1,3-тіазол-5-іл)піперазин (середні значення lg GI50 = -5.66, lg TGI
= -5.26, lg LC50 = -4.83) та 1-(2,4-біс((4-метилфеніл)сульфоніл)-1,3-тіазол-5-іл)піперазин (середні значення lg GI50 = -5.67, lg TGI = -5.21,
lg LC50 = -4.67) виявили найвищу інгібуючу активність. Отримані результати свідчать про перспективність пошуку серед ди- та
трифункціональнозаміщених похідних 1,3-тіазолу нових протиракових препаратів.
Ключові слова: 1,3-тіазол; протиракова активність; інгібітори росту; цитостатична активність; цитотоксична активність.
Notes
Acknowledgements. We would like to thank National Cancer Institute, Bethesda, MD, US for the anticancer activity investigations and Enamine Ltd. for the material and technical support.
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| id | oai:ojs2.bioorganica.com.ua:article-2 |
| institution | Ukrainica Bioorganica Acta |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-20T01:00:43Z |
| publishDate | 2020 |
| publisher | V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine |
| record_format | ojs |
| resource_txt_mv | bioorganicacomua/2a/f1d621aa9f8226fe769ac8f344302d2a.pdf |
| spelling | oai:ojs2.bioorganica.com.ua:article-22026-07-19T14:56:52Z Anticancer evaluation of di- and trifunctional substituted 1,3-thiazoles Оцінка протиракової активності ди- та трифункціональнозаміщених 1,3-тіазолів Turov, Kostyantyn V. Mitiukhin, Оleg P. Chumachenko, Svitlana A. Zyabrev, Vladimir S. Brovarets, Volodymyr S. 1,3-thiazole anticancer activity growth inhibitor cytostatic activity cytotoxic activity 1,3-тіазол протиракова активність інгібітори росту цитостатична активність цитотоксична активність Anticancer activity of a series of polyfunctional substituted 1,3-thiazoles has been studied within the international scientific program “NCI-60 Human Tumor Cell Lines Screen”. Screening was performed in vitro on 60 cell lines of lungs, kidneys, CNS, ovaries, prostate, and breast cancer, epithelial cancer, leukemia, and melanoma. The most effective compounds were those with a piperazine substituent at C2 of the 1,3-thiazole cycle: 1-(4-((4-methylphenyl)-sulfonyl)-2-phenyl-1,3-thiazol-5-yl)piperazine (average lg GI50 = -5.87, lg TGI = -5.54, lg LC50 = -5.21), 1-(2-(3,5-dimethyl-1H-pyrazol-1-yl)-4-((4-methylpheyl)sulfonyl)-1,3-thiazol-5-yl)piperazine (average lg GI50 = -5.66, lg TGI = -5.26, lg LC50 = -4.83), and 1-(2,4-bis((4-methylphenyl)sulfonyl)-1,3-thiazol-5-yl)piperazine (average lg GI50 = -5.67, lg TGI = -5.21, lg LC5050 = -4.67). Cинтезовано ряд ди- та трифункціональнозаміщених 1,3-тіазолів з використанням в якості вихідних сполук 1-R-3-тозил-1,4,4-трихлоро-2-аза-1,3-бутадієнів або 1-тозил-2,2-дихлороетенілізотіоціанату. Скринінгові дослідження протиракової активності синтезованих сполук проведено in vitro на 60 лініях ракових клітин людини: лейкемії (лінії CCRF-CEM, HL-60 (TB), K-562, MOLT-4, RPMI-8226, SR), меланоми (лінії LOX IMVI, MALME-3M, M14, MDA-MB-435, SK-MEL-2, SK-MEL-28, SK-MEL-5 , UACC-257, UACC-62), раку легенів (лінії A549/ATCC, EKVX, HOP-62, HOP-92, NCI-H226, NCI-H23, NCI-H322M, NCI-H460, NCI-H522), товстої кишки (лінії COLO 205, HCC-2998, HCT-116, HCT-15, HT29, KM12, SW-620), мозку (лінії SF-268, SF-295, SF-539, SNB-19, SNB-75, U251), яєчників (лінії IGROV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, NCI/ADR-RES, SK-OV-3), нирок (лінії 786-0, A498, ACHN, CAKI-1, RXF 393, SN12C, TK-10, UO-31), простати (лінії PC-3, DU-145) і грудей (лінії MCF7, MDA-MB-231/ATCC, HS 578T, BT-549, T- 47D, MDA-MB-468) при концентрації 1·10-5 М. В результаті визначено відсоток росту (GР) клітин ліній раку у порівнянні з контролем (контроль – 100%). Поглиблений in vitro скринінг сполук полягав у вивченні її протипухлинного ефекту в п`яти концентраціях при 10-кратному розведенні (10-4-10-8 М). У результаті експерименту розраховано 3 дозозалежні параметри (GI50, TGI, LC50). Серед даних сполук 1-(4-((4-метилфеніл)сульфоніл)-2-феніл-1,3-тіазол-5-іл)піперазин (середні значення lg GI50 = -5.87, lg TGI = -5.54, lg LC50 = -5.21), 1-(2-(3,5-диметил)-1Н-піразол-1-іл)-4-((4-метилфеніл)сульфоніл)-1,3-тіазол-5-іл)піперазин (середні значення lg GI50 = -5.66, lg TGI = -5.26, lg LC50 = -4.83) та 1-(2,4-біс((4-метилфеніл)сульфоніл)-1,3-тіазол-5-іл)піперазин (середні значення lg GI50 = -5.67, lg TGI = -5.21, lg LC50 = -4.67) виявили найвищу інгібуючу активність. Отримані результати свідчать про перспективність пошуку серед ди- та трифункціональнозаміщених похідних 1,3-тіазолу нових протиракових препаратів V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2020-06-30 Article Article application/pdf https://bioorganica.com.ua/index.php/journal/article/view/2 10.15407/bioorganica2020.01.002 Ukrainica Bioorganica Acta; Vol. 15 No. 1 (2020): Ukrainica Bioorganica Acta; 2-11 Ukrainica Bioorganica Acta; Том 15 № 1 (2020): Ukrainica Bioorganica Acta; 2-11 1814-9766 1814-9758 10.15407/bioorganica2020.01 en https://bioorganica.com.ua/index.php/journal/article/view/2/1 Copyright (c) 2020 Kostyantyn V. Turov, Оleg P. Mitiukhin, Svitlana A. Chumachenko, Vladimir S. Zyabrev, Volodymyr S. Brovarets https://creativecommons.org/licenses/by/4.0 |
| spellingShingle | 1,3-тіазол протиракова активність інгібітори росту цитостатична активність цитотоксична активність Turov, Kostyantyn V. Mitiukhin, Оleg P. Chumachenko, Svitlana A. Zyabrev, Vladimir S. Brovarets, Volodymyr S. Оцінка протиракової активності ди- та трифункціональнозаміщених 1,3-тіазолів |
| title | Оцінка протиракової активності ди- та трифункціональнозаміщених 1,3-тіазолів |
| title_alt | Anticancer evaluation of di- and trifunctional substituted 1,3-thiazoles |
| title_full | Оцінка протиракової активності ди- та трифункціональнозаміщених 1,3-тіазолів |
| title_fullStr | Оцінка протиракової активності ди- та трифункціональнозаміщених 1,3-тіазолів |
| title_full_unstemmed | Оцінка протиракової активності ди- та трифункціональнозаміщених 1,3-тіазолів |
| title_short | Оцінка протиракової активності ди- та трифункціональнозаміщених 1,3-тіазолів |
| title_sort | оцінка протиракової активності ди- та трифункціональнозаміщених 1,3-тіазолів |
| topic | 1,3-тіазол протиракова активність інгібітори росту цитостатична активність цитотоксична активність |
| topic_facet | 1,3-thiazole anticancer activity growth inhibitor cytostatic activity cytotoxic activity 1,3-тіазол протиракова активність інгібітори росту цитостатична активність цитотоксична активність |
| url | https://bioorganica.com.ua/index.php/journal/article/view/2 |
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