Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles
The aim of present research was the investigation of antioxidant and antiexudative activities of the series of thiopyrano[2,3-d]thiazoles synthesized based on cinnamic acid amides. Methods. Organic synthesis; spectral methods; free radical scavenging assay (DPPH test); evaluation of antiexudative ac...
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irk-123456789-1524442019-06-13T01:26:24Z Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles Lozynskyi, A.V. Kaminskyy, D.V. Romanchyshyn, Kh.B. Semenciv, N.G. Ogurtsov, V.V. Nektegayev, I.O. Lesyk, R.B. Bioorganic Chemistry The aim of present research was the investigation of antioxidant and antiexudative activities of the series of thiopyrano[2,3-d]thiazoles synthesized based on cinnamic acid amides. Methods. Organic synthesis; spectral methods; free radical scavenging assay (DPPH test); evaluation of antiexudative activity (carrageenan oedema model in rats). Results. The evaluation of the free radicals scavenging activity and antiexudative activity of series of the 2-oxo-5-phenyl-7-aryl(hetaryl)-3,7-dihydro-2H-thiopyrano[2,3-d]thiazole-6-carboxylic acid amides was performed. Among the tested compounds, rel-(5R,6S,7S)-N-(4-methylphenyl)-7-(4-methylphenyl)-2-oxo-5-phenyl-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]thiazole-6-carboxamide possessed the highest level of both activities. The experimental data most probably indicate a pronounced effect of methyl groups (phenyl fragments) on the realization of the anti-inflammatory and antioxidant effects and allow a suggestion about the antiradical mechanism of anti-inflammatory activity of the target compounds. Conclusions. The anti-inflammatory and free radicals scavenging activities of some tiopyrano[2,3-d]thiazoles have been established and the most active compounds were identified. Some findings of the structure-activity relationship were set up. Мета даного дослідження полягала у вивченні антиоксидантної та антиексудативної активності похідних тіопірано [2,3-d]тіазолу одержаних на основі амідів коричної кислоти. Методи. Органічний синтез; спектральні методи; оцінка радикал поглинаючої (DPPH тест) та антиексудативної активностей (карагенінової модель набряку лапи щура). Результати. Проведено визначення радикал поглинаючої та антиексудативної активності амідів 2-оксо-5-феніл-7-арил(гетерил)-3,7-дигідро-2Н-тіопірано[2,3-d]тіазол-6-карбонових кислот. Серед тестованих сполук rel-(5R,6S, 7S)-N-(4-метилфеніл)-7-(4-метилфеніл)-2-оксо-5-феніл-3,5,6,7-тетрагідро-2H-тіопірано[2,3-d]тіазол-6-карбоксамід характеризувався максимальними значеннями обох видів активності. Отримані дані, очевидно, свідчать про виражений вплив метильних груп (у фенільних фрагментах) на реалізацію протизапального та антиоксидантного ефектів та дозволяють припустити антирадикальний механізм протизапальної активності сполук даного ряду. Висновки. Встановлено протизапальну та антирадикальну активності ряду тіопірано[2,3-d]тіазолів, ідентифіковано сполуки з високим рівнем активності та проаналізовані деякі аспекти взаємозв’язку структура-активність. Цель данного исследования заключалась в изучении антиоксидантной и антиэкссудативной активности производных тиопирано[2,3-d]тиазола полученых на основе амидов коричной кислоты. Методы. Органический синтез; спектральные методы; оценка радикал поглощающей (DPPH тест) и антиэкссудативной активностей (карагениновая модель отека лапы крысы). Результаты. Проведено исследование радикал поглощающей активности и антиэкссудативного активности амидов 2-оксо-5-фенил-7-арил(гетерил)-3,7-дигидро-2Н-тиопирано[2,3-d]тиазол-6-карбоновых кислот. Среди испытуемых соединений rel-(5R,6S,7S)-N-(4-метилфенил)-7-(4-метилфенил)-2-оксо-5-фенил-3,5,6,7-тетрагидро-2H-тиопирано[2,3-d]тиазол-6-карбоксамид характеризировался максимальными значениями обоих видов активности. Полученные данные, по-видимому, свидетельствуют о выраженном влиянии метильных групп (в фенильных фрагментах) на реализацию противовоспалительного и антиоксидантного эффектов и позволяют предположить антирадикальний механизм противовоспалительной активности соединений данного ряда. Выводы. Установлено противовоспалительную и антирадикальную активности ряда тиопирано[2,3-d]тиазолов, идентифицировано соединения с высоким уровнем активности, а также проанализированы некоторые аспекты взаимосвязи структура-активность. 2015 Article Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles / A.V. Lozynskyi, D.V. Kaminskyy, Kh.B Romanchyshyn., N.G. Semenciv, V.V. Ogurtsov, I.O. Nektegayev, R.B. Lesyk // Вiopolymers and Cell. — 2015. — Т. 31, № 2. — С. 131-137. — Бібліогр.: 30 назв. — англ. 0233-7657 DOI: http://biopolymers.org.ua/doi/bc.0008D8 http://dspace.nbuv.gov.ua/handle/123456789/152444 547.818:547.489.4:542.91:615.359 en Вiopolymers and Cell Інститут молекулярної біології і генетики НАН України |
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Bioorganic Chemistry Bioorganic Chemistry |
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Bioorganic Chemistry Bioorganic Chemistry Lozynskyi, A.V. Kaminskyy, D.V. Romanchyshyn, Kh.B. Semenciv, N.G. Ogurtsov, V.V. Nektegayev, I.O. Lesyk, R.B. Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles Вiopolymers and Cell |
| description |
The aim of present research was the investigation of antioxidant and antiexudative activities of the series of thiopyrano[2,3-d]thiazoles synthesized based on cinnamic acid amides. Methods. Organic synthesis; spectral methods; free radical scavenging assay (DPPH test); evaluation of antiexudative activity (carrageenan oedema model in rats). Results. The evaluation of the free radicals scavenging activity and antiexudative activity of series of the 2-oxo-5-phenyl-7-aryl(hetaryl)-3,7-dihydro-2H-thiopyrano[2,3-d]thiazole-6-carboxylic acid amides was performed. Among the tested compounds, rel-(5R,6S,7S)-N-(4-methylphenyl)-7-(4-methylphenyl)-2-oxo-5-phenyl-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]thiazole-6-carboxamide possessed the highest level of both activities. The experimental data most probably indicate a pronounced effect of methyl groups (phenyl fragments) on the realization of the anti-inflammatory and antioxidant effects and allow a suggestion about the antiradical mechanism of anti-inflammatory activity of the target compounds. Conclusions. The anti-inflammatory and free radicals scavenging activities of some tiopyrano[2,3-d]thiazoles have been established and the most active compounds were identified. Some findings of the structure-activity relationship were set up. |
| format |
Article |
| author |
Lozynskyi, A.V. Kaminskyy, D.V. Romanchyshyn, Kh.B. Semenciv, N.G. Ogurtsov, V.V. Nektegayev, I.O. Lesyk, R.B. |
| author_facet |
Lozynskyi, A.V. Kaminskyy, D.V. Romanchyshyn, Kh.B. Semenciv, N.G. Ogurtsov, V.V. Nektegayev, I.O. Lesyk, R.B. |
| author_sort |
Lozynskyi, A.V. |
| title |
Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles |
| title_short |
Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles |
| title_full |
Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles |
| title_fullStr |
Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles |
| title_full_unstemmed |
Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles |
| title_sort |
screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| publishDate |
2015 |
| topic_facet |
Bioorganic Chemistry |
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http://dspace.nbuv.gov.ua/handle/123456789/152444 |
| citation_txt |
Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles / A.V. Lozynskyi, D.V. Kaminskyy, Kh.B Romanchyshyn., N.G. Semenciv, V.V. Ogurtsov, I.O. Nektegayev, R.B. Lesyk // Вiopolymers and Cell. — 2015. — Т. 31, № 2. — С. 131-137. — Бібліогр.: 30 назв. — англ. |
| series |
Вiopolymers and Cell |
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131
ISSN 0233-7657
Biopolymers and Cell. 2015. Vol. 31. N 2. P. 131–137
doi: http://biopolymers.org.ua/doi/bc.0008D8
Bioorganic chemistry
UDC: 547.818:547.489.4:542.91:615.359
Screening of antioxidant and anti-infl ammatory
activities among thiopyrano[2,3-d]thiazoles
A. V. Lozynskyi, D. V. Kaminskyy, Kh. B. Romanchyshyn,
N. G. Semenciv, V. V. Ogurtsov, I. O. Nektegayev, R. B. Lesyk
Danylo Halytsky Lviv National Medical University
69, Pekarska Str., Lviv, Ukraine, 79010
dr_r_lesyk@org.lviv.net, roman.lesyk@gmail.com
The aim of present research was the investigation of antioxidant and antiexudative activities of the series
of thiopyrano[2,3-d]thiazoles synthesized based on cinnamic acid amides. Methods. Organic synthesis;
spectral methods; free radical scavenging assay (DPPH test); evaluation of antiexudative activity (car-
rageenan oedema model in rats). Results. The evaluation of the free radicals scavenging activity and
antiexudative activity of series of the 2-oxo-5-phenyl-7-aryl(hetaryl)-3,7-dihydro-2H-thiopyrano[2,3-d]
thiazole-6-carboxylic acid amides was performed. Among the tested compounds, rel-(5R,6S,7S)-N-(4-
methylphenyl)-7-(4-methylphenyl)-2-oxo-5-phenyl-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]thiazole-6-
carboxamide possessed the highest level of both activities. The experimental data most probably indicate
a pronounced effect of methyl groups (phenyl fragments) on the realization of the anti-infl ammatory and
antioxidant effects and allow a suggestion about the antiradical mechanism of anti-infl ammatory activity
of the target compounds. Conclusions. The anti-infl ammatory and free radicals scavenging activities of
some tiopyrano[2,3-d]thiazoles have been established and the most active compounds were identifi ed.
Some fi ndings of the structure-activity relationship were set up.
K e y w o r d s: thiopyrano[2,3-d]thiazoles, antioxidant activity, antiexudative activity.
© 2015 A. V. Lozynskyi et al.; Published by the Institute of Molecular Biology and Genetics, NAS of Ukraine on behalf of Biopolymers and Cell.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/),
which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited
Introduction
The oxidant and free radical processes are in focus
of the research. The reactive oxygen and nitrogen
species such as hydroxyl and peroxyl radicals, the
superoxide anion etc., are constantly produced as a
result of metabolic reactions in living systems and
are involved in numerous processes, both normal
and pathological [1]. Living systems are protected
from the oxidative damage by these reactive species
by enzymes (for instance, superoxide dismutase,
glutathione peroxidase) and by antioxidant com-
pounds such as ascorbic acid, tocopherols, and caro-
tenoids, etc. [1, 2]. However, when the free-radical
production exceeds the antioxidant capacity, these
radical species attack macromolecules, thus damag-
ing structural integrity and function of cell mem-
branes, enzymes, and genetic material. A growing
body of evidence indicates that various pathological
conditions, including cardiovascular disease, arthri-
tis, infl ammation, cancer, and Alzheimer's disease
are associated, at least in part, with the damaging ef-
fects of uncontrolled free-radicals production [3, 4].
Thus, many biologically active compounds, espe-
cially natural, may provide the protection against
mentioned processes through multiple effects, which
are still poorly understood [5–7]. These compounds
may act as antioxidants by reacting with free radicals
and thus interrupting the propagation of new free
radical species, by chelating metal ions, etc. They
132
A. V. Lozynskyi, D. V. Kaminskyy, Kh. B. Romanchyshyn et al.
also may protect against oxidant-mediated infl am-
mation and tissue damage by a virtue of their ability
not only to scavenge free radicals but also to inhibit
the activation of NF-kB (and possibly other oxidant-
sensitive transcription factors) [4, 5] and improve
certain immune responses [8].
On the other hand, many synthetic heterocycles
possess similar biological profi les. For instance,
4-thia zolidinones and related heterocycles showed
the antiinfl ammatory, antitumor, antitrypanosomal,
antidiabetic activities, which often are associated
with the antioxidant effect [9–11]. Majority of 4-
thiazolidione-based lead-compounds and drug-can-
didates belong to the 5-ylidene-4-thiazolidinone
subtype and have many advantages in the drug dis-
covery [9, 12–16]. At the same time, they are also
characterized by some negative features. 5-Ylide-
ne-4-thiazolidinones can be considered as electro-
philic and potentially reactive substances due to the
possible Michael addition of the nucleophilic pro-
tein residues to the exocyclic double bond. This
characterizes 5-arylidene-4-thiazolidinones as the
frequent hitters or pan assay interference com-
pounds that are useless in the modern drug discov-
ery process because of low selectivity [17].
One of the possible solutions of such confusion
may be the annealing of the mentioned 5-ylidene-4-
thiazolidinones into the fused heterocycles. These
fused 4-thiazolidinone-based derivatives and in par-
ticular thiopyrano[2,3-d]thiazoles are considered as
the cyclic isosteric mimetics of their synthetic pre-
cursors – 5-ylidene-4-thiazolidinones without the
Michael accepting functionalities [19, 20]. Moreover,
design of the mentioned fused heterocycles em-
ployed the combination of thiazolidinones and other
chemicals including those possessing signifi cant bi-
ological activity, for instance cinnamic acid and its
derivatives (Fig. 1.), that can be treated as a benefi t
in the hybride molecules design.
Therefore, as the continuation of our previous
studies [19–22] in the fi eld of biologically active
fused 4-thiazolidinone-based heterocycles the aim
of the manuscript was the search for new compounds
with antioxidant and antiexudative activities among
thiopyrano[2,3-d]thiazoles.
Materials and Methods
All chemicals were of the analytical grade and com-
mercially available. All reagents and solvents were
used without further purifi cation and drying.
Chemistry. The raw of 2-oxo-5-phenyl-7-aryl(he-
taryl)-3,7-dihydro-2H-thiopyrano[2,3-d]thiazole-6-
carbocyclic acid amides (1-10) for antioxidant and
anti-infl ammatory screening was synthesized by us
previously (Scheme) [22]. Starting cinnamic acid
was transformed into corresponding acid chloride and
then converted into appropriate amides. The 5-aryli-
dene-4-thioxo-2-thiazolidinones were synthesized via
Knoevenagel condensation of 4-thioxo-2-thiazolidi-
none with aldehydes (ethanol medium in the pres-
ence of ethylenediaminediacetate) [19]. The fi nal
phase was the hetero-Diels-Alder reaction, with re-
gioselectively and diastereoselectively yielded target
rel-(5R,6S,7S)-2-oxo-5-phe nyl-7-aryl(hetaryl)-3,7-
Fig. 1. Background for target compounds design
133
Antioxidant/anti-infl ammatory thiopyranothiazoles
dihydro-2H-thio py ra no[2, 3-d] thiazole-6-carbocy-
clic acid amides.
rel-(5R,6S,7S)-N-(4-Methylphenyl)-7-(4-
methoxyphenyl)-2-oxo-5-phenyl-3,5,6,7-tetrahydro-
2H-thiopyrano[2,3-d]thiazole-6-carboxamide (11).
A mixture of 5-(4-metoxybenzylidene)-4-thioxo-
2-thiazolidinone (5 mmol) and N-(4-methylphenyl)-
3-phenylacrylamide (5.5 mmol) was refl uxed for 5
h with a catalytic amount of hydroquinone (2–3 mg)
in 15 mL of glacial acetic acid and left overnight at
rt. The obtained product was collected by fi ltration,
washed with water, methanol, diethyl ether, and re-
crystallized from the ethanol. Yield: 70%, mp 234-
236 C. 1H NMR (400 MHz, DMSO-d6) : 2.16 (s,
3H, CH3), 3.44 (t, 1H, J = 10.4 Hz, 6-H), 4.30 (d, 1H,
J = 10.4 Hz, 7-H), 4.70 (d, 1H, J = 10.4 Hz, 5-H),
6.75 (d, 2H, J = 8.4 Hz, arom.), 6.83 (d, 2H, J = 8.4
Hz, arom.), 7.32 (d, 2H, J = 7.2 Hz, arom.), 7.46 (d, 2H,
J = 7.2 Hz, arom.), 9.23 (s, 1H, NH), 11.29 (s, 1H, NH).
13C NMR (100 MHz, DMSO-d6) : 20.3, 45.0, 48.5,
55.8, 107.5, 119.1, 119.8, 120.4, 128.3, 128.4, 128.5,
128.6, 130.2, 132.0, 132.7, 134.9, 136.2, 139.3, 167.9,
170.4. Anal.Calcd for C27H24N2O3S2, % C, 66.37; H,
4.95; N, 5.73. Found, %: C, 66.50; H, 4.90; N, 5.62.
Pharmacology. The synthesized compounds were
evaluated for their antioxidant (DPPH free radical
scavenging assay) and antiexudative activity on the
carrageenan oedema model in rats.
Free radical scavenging assay. The scavenging ef-
fect of the synthesized compounds on the DPPH (1,1-
diphenyl-2-picrylhydrazyl radical) was evaluated ac-
cording to the Blois method [23]. The solution of DPPH
(150 μM) in ethanol (4 mL) was mixed with the tested
compound or ascorbic acid as the referent compound
(250 μM) solution in ethanol (0.2 mL). The reaction
mixture was thoroughly mixed and incubated 30 min
at rt. in the dark. A decrease in absorbance of the mix-
ture (in comparision with the sample which contains
only DPPH solution) was measured at 540 nm. All
tests and analyses were undertaken in three replicates
and the results avera ged. The scavenging activity was
calculated: (%) = ([ADPPH – As] / ADPPH) × 100 %, whe-
re: ADPPH is an absorbance of DPPH solution, As is an
absorbance of the tested sample.
Antiexudative assay. For antiexudative test the
male rats weighing 180–220 g were used. The carra-
genan-induced hind paw oedema was produced by
the method of Winter et al. [24]. Carrageenan solu-
tion (1.0 % in sterile 0.9 % NaCl) was injected sub-
cutaneosly into the subplanar region of the hind paw
(0.1 mL to each paw) 1h after administration of the
test compound. The synthesized compounds were
intraperitoneally injected in a dose 100 mg/kg (in sa-
line solution with one drop of Tween-80TM). Dic lo-
fenac sodium (10 mg/kg) and ketorolac tromethami-
ne (10 mg/kg) were used as reference compounds.
Control rats received only saline solution with one
drop of Tween-80TM. The hind paw volume was
measured with an electronic onkograph immediately
before and 4h after carrageenan injection. The effect
of test compounds on a decrease of paw oedema was
compared with that control. The antiexudative activ-
ity was expressed as a decrease of rats paw oedema
and was given in percentage.
Results and Discussion
The structure of new thiopyrano[2,3-d]thiazoles (fi g.
2) was designed based on the cinnamic acids deriva-
Scheme. General synthetic scheme
134
A. V. Lozynskyi, D. V. Kaminskyy, Kh. B. Romanchyshyn et al.
tives and the mentioned 5-ylidene-4-thiazolidino-
nes. The synthetic protocol involved the regiose-
lective and diastereoselective hetero-Diels-Alder
reaction. The synthesized compounds were screened
for anti-infl ammatory and antioxidant activities.
The re is a thesis that an increase of reactive radical
species levels causes the development of infl amma-
tion along with the antioxidant effect of many anti-
infl ammatory agents. Therefore, it is apparent that
in addition to promoting cytotoxicity, reactive oxy-
gen metabolites may also initiate and/or amplify
infl ammation via the upregulation of several differ-
ent genes involved in the infl ammatory response,
such as those that code for proinfl ammatory cy-
tokines and adhesion molecules [4].
Consequently, the compounds with antioxidant
properties could be expected to offer protection in
the infl ammation process. It is therefore evident that
the treatment of the above mentioned pathophysiolo-
gies could benefi t from the use of drugs with both
antioxidant and anti-infl ammatory activities. It has
already been proven for a number of commercially
available non-steroidal anti-infl ammatory drugs
(NSAIDs), for example, tolfenamic acid which si-
multaneously possess radical scavenging properties
S
N
HS
O
O
N
H
N
S
Ph
S
N
HS
O
O
N
O
Me
Ph
S
N
HS
O
O
N
H
OH
Cl
Ph
S
N
HS
O
O
N
H
R
Cl
Ph
OH
NH2SO2
Cl
Me
S
N
HS
O
O
N
H
R
Ph
Me
S
N
HS
O
O
N
H
O
Me
Ph
Me
1
9
2
10
R =
2-5 6-8
11
3, 6
4, 7
5, 8
Fig. 2. The structure of compounds involved into the study
Table 1. Antioxidant activity of thiopyrano[2,3-d]thiazoles
Compound Absorbance
of a sample Inhibition, %
4 0.750 ± 0.016 3.90
6 0.748 ± 0.014 4.04
7 0.354 ± 0.006 54.57
8 0.748 ± 0.015 4.11
9 0.739 ± 0.016 5.27
11 0.742 ± 0.015 4.86
Ascorbic acid 0.533 ± 0.012 31.70
Table 2. Antiexudative activity of the tested
of thiopyrano[2,3-d]thiazoles
Сompound Paw oedema
volume, %
Inhibition of paw
edema over control, %
– 96.2 ± 3.78 –
1 86.2 ±4.32 10.4
2 85.3 ± 4.21 11.3
3 57.6 ± 2.80 40.1
4 63.4 ± 3.11 34.1
5 69.2 ± 3.40 28.0
6 80.4 ± 4.06 16.4
7 52.4 ± 2.61 45.5
10 64,3 ± 3.20 33.1
Diclofenac 54.6 ± 2.53 43.2
Ketorolac 56.6 ± 2.60 41.1
135
Antioxidant/anti-infl ammatory thiopyranothiazoles
[25, 26]. Additionally, several thiazolidinone deriva-
tives are also pronounced anti-infl ammatory and
antioxidant agents and might be an exellent basis in
searching for the drug-like molecules [27].
To investigate some aspects of the structure-activ-
ity relationship among thiopyrano[2,3-d]thiazoles,
the antioxidant activity was assessed by the DPPH-
free radicals cavenging assay and summarized in
Table 1.
Among the tested compounds the rel-(5R,6S,7S)-
N-(4-methylphenyl)-7-(4-methylphenyl)-2-oxo-5-
phenyl-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]
[1,3]thiazole-6-carboxamide (7) was found to be the
most active; for other derivatives, a slight antioxi-
dant activity was observed. The comparison of the
activity of compounds bearing different amide frag-
ments (compounds 4, 6, 7 & 9) allowed the sugges-
tion that the presence of methyl groups (including
amide fragment) in compound 7 was crucial for the
antioxidant activity realization. The same effect was
observed in fl avonoids row, where the methyl de-
rivatives were much more active in comparison with
the derivatives bearing other substituents [28]. This
effect is also associated with improved lipophilicity
parameter [29]. Moreover, the presence of electron
donating groups (especially methyls) at the aromatic
core has previously been shown to infl uence strongly
the redox potential of α,β-unsaturated aromatic com-
pounds. The altered reduction potential of these
compounds has an effect on the lipid peroxidation
reactions, in which they can participate, and this, in
turn, alters their ability to scavenge deleterious oxy
radicals [30]. The replacement of the methyl group
in the aryl fragment (position 7 of the main core)
(compounds 7, 8 & 11) to the methoxy group or a
halogen atom leads to the loss of activity.
The in vivo anti-infl ammatory effect of the tested
compounds was assessed by using the functional mo-
del of carrageenan-induced rat paw oedema (Table 2).
All tested compounds exhibited different protec-
tion against the carrageenan-induced paw edema. The
compounds 3 and 7 were the most active among the
tested thiopyrano[2,3-d]thiazoles. The antiexudative
activity comparable to the reference drugs was ob-
served in the compounds with two methyl groups (7)
or in the presence of methyl and sulfamoyl groups
(3). The presence of other group in the molecule led
to a decrease in the activity level. The comparison of
anti-radical and anti-infl ammatory activities allows
us to assume the involvement of antioxidant mode in
the development of thiopyrano[2,3-d]thiazoles anti-
infl ammatory action.
Conclusion
The present study has shown that certain thio py ra-
no[2,3-d]thiazoles possess low to moderate anti-
infl ammatory and antioxidant activities, whereas
the compound 7 was found to be a promising free
radicals scavenger. The anti-infl ammatory assay
led to the identifi cation of two active molecules
(compo unds 3 & 7). These compounds constitute
an interesting template for the design of new syn-
thetic NSAIDs. Despite that the anti-infl ammatory
mechanism was not elucidated, the mode of anti-
infl ammatory action of the synthesized compounds
seems to be related with their radical scavenging
activity.
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Скринінг антиоксидантної та протизапальної
активності похідних тіопірано[2,3-d]тіазолу
А. В. Лозинський, Д. В. Камінський,
Х. Б. Романчишин, Н. Г. Семенців, В. В. Огурцов,
І. О. Нєктєгаєв, Р. Б. Лесик
Мета даного дослідження полягала у вивченні антиокси-
дантної та антиексудативної активності похідних тіопі ра-
но [2,3-d]тіазолу одержаних на основі амідів коричної кис-
лоти. Методи. Органічний синтез; спектральні методи;
оцін ка радикал поглинаючої (DPPH тест) та антиексуда-
тивної активностей (карагенінової модель набряку лапи
щура). Резу ль та ти. Проведено визначення радикал погли-
наючої та антиексудативної активності амідів 2-оксо-5-
феніл-7-арил(ге те рил)-3,7-дигідро-2Н-тіопірано[2,3-d]
тіазол-6-карбонових кислот. Серед тестованих сполук rel-
(5R,6S, 7S)-N-(4-ме тил феніл)-7-(4-метилфеніл)-2-оксо-5-
феніл-3,5,6,7-тетрагідро-2H-тіопірано[2,3-d]тіазол-6-
карбоксамід характеризувався максимальними значеннями
обох видів активності. Отримані дані, очевидно, свідчать
про виражений вплив метильних груп (у фенільних фраг-
ментах) на реалізацію протизапального та антиоксидант-
ного ефектів та дозволяють припустити антирадикальний
механізм протизапальної активності сполук даного ряду.
137
Antioxidant/anti-infl ammatory thiopyranothiazoles
Висновки. Вста новлено протизапальну та антирадикаль-
ну активності ряду тіо пі ра но[2,3-d]тіазолів, ідентифікова-
но сполуки з високим рівнем активності та про аналізовані
деякі аспекти взає мо зв’язку структура-ак тив ність.
Ключов і слова: тіопірано[2,3-d]тіазоли, антиоксидант-
на, антиексудативна активність.
Скрининг антиоксидантной
и противовоспалительной активности
производных тиопирано[2,3-d]тиазола
А. В. Лозинский, Д. В. Каминский,
Х. Б. Романчишин, Н. Г. Семенцив, В. В. Огурцов,
И. А. Нектегаев, Р. Б. Лесык
Цель данного исследования заключалась в изучении анти-
оксидантной и антиэкссудативной активности производ-
ных тиопирано[2,3-d]тиазола полученых на основе амидов
коричной кислоты. Методы. Органический синтез; спек-
тра льные методы; оценка радикал поглощающей (DPPH
тест) и антиэкссудативной активностей (карагениновая
мо дель отека лапы крысы). Результаты. Проведено иссле-
дование радикал поглощающей активности и антиэкссуда-
тивного активности амидов 2-оксо-5-фенил-7-арил (гете-
рил)- 3,7-ди гид ро-2Н-тиопирано[2,3-d]тиазол-6-карбоновых
кислот. Среди испытуемых соединений rel-(5R,6S,7S)-N-
(4-метилфенил)-7-(4-метилфенил)-2-оксо-5-фенил-3,5,6,7-
тетрагидро-2H-тиопирано[2,3-d]тиазол-6-карбоксамид ха-
рактеризировался максимальными значениями обоих ви-
дов активности. По лу ченные данные, по-видимому, свиде-
тельствуют о выраженном влиянии метильных групп (в
фенильных фрагментах) на реализацию противовоспали-
тельного и антиоксидан т ного эффектов и позволяют пред-
положить антирадикальний механизм противовоспалите-
льной активности соединений данного ряда. Выводы. Ус-
тановлено противовоспалительную и антирадикальную ак-
тивности ряда тио пирано[2,3-d]тиазолов, идентифицировано
соединения с высоким уровнем активности, а также про-
анализированы некоторые аспекты взаимосвязи структу-
ра-активность.
Ключевые слова: тиопирано[2,3-d]тиазолы, антиокси-
дантная, антиэкссудативная активность.
Received 17.01.2015
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