SYNTHESIS AND ANTI-INFLAMMATORY PROPERTIES OF SOME C5 SUBSTITUTED 3-METHYL-4-THIOXO-THIAZOLIDIN-2-ONES
DOI:
https://doi.org/10.11603/mcch.2410-681X.2020.i4.11735Keywords:
organic synthesis, 3-methyl-4-thioxo-thiazolidin-2-one, azo coupling, anti-inflammatory activityAbstract
Introduction. The study of the reactivity of 4-thiazolidone derivatives and the implementation of their chemical transformations is a promising area for the search for new biologically active substances. This is due to the wide range of biological activity of this class of compounds, as well as the presence of a number of reactive centers, which allows for various modifications of the original structure. Taking into account these circumstances, the synthesis of new substances as potential drug-like molecules among this class of compounds is relevant.
The aim of the study – to synthesize some C5 substituted derivatives of 3-methyl-4-thioxo-thiazolidin-2-one for pharmacological screening in vivo of their anti-inflammatory activity.
Research Methods. Organic synthesis, 1H NMR spectroscopy, elemental analysis, pharmacological screening were performed.
Results and Discussion. The synthetic part of the work consisted in the structural modification of 3-methyl-4-thioxo-thiazolidin-2-one. The active methylene group at the C5 position of the said scafold exhibits CH-acidic properties and allows to carry out the azo coupling reaction with aryldiazonium salts to give the corresponding 3-methyl-5-(aryl-hydrazones)-4-thioxo-thiazolidin-2-ones. The structure of the obtained compounds and the interpretation of the performed chemical studies were confirmed by the data of elemental analysis and 1H NMR spectroscopy. The study of the effect of synthesized substances on the course of the exudative phase of inflammation was performed on the basis of the carrageenan model of inflammatory edema of the paws of white rats. The presence of an inflammatory reaction was established with a change in the volume of the limb by the oncometric method at the beginning of the experiment and 4 hours after the introduction of the phlogogenic agent. For comparison, the anti-inflammatory effect of Ibuprofen was studied under similar conditions. The synthesized compounds have anti-inflammatory properties, and some of them in terms of activity are close to or exceed the comparison drug.
Conclusions. As a result of structural modification of 3-methyl-4-thioxo-thiazolidin-2-one at position C5, a series of novel 3-methyl-5-(aryl-hydrazone)-4-thioxo-thiazolidin-2-ones was synthesized. The studies carried out on the anti-inflammatory activity of the synthesized compounds demonstrate the potential to search for anti-inflammatory agents among this class of compounds. We are continuing to study the reactivity and chemical transformations with the prospect of studying the biological activity of this class of compounds.
References
Pirlamarla, P., & Bond, R.M. (2016). FDA labeling of NSAIDs: Review of nonsteroidal anti-inflammatory drugs in cardiovascular disease. Trends Cardiovascular Medicine, 26, 675-680.
Brenner, P., & Krakauer, T. (2003). Regulation of Inflammation: A review of recent advances in anti- inflammatory strategies. Current Medicinal Chemistry, 2, 274-283.
Bacchi, S., Palumbo, P., Sponta, A., & Coppolino, M. (2012).Clinical pharmacology of non-steroidal anti-inflammatory drugs: a review. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 11, 52-64.
Kaur, S., Ramandeep, M., Rohit, K., Kapil, B., Singh, V., Shankarc, R., Kaura, R., & Rawa, R. (2017). Synthetic and medicinal perspective of thiazolidinones: A review. Bioorganic Chemistry, 75, 406-423.
Kaminskyy, D., Kryshchyshyn, A., & Lesyk, R. (2017). 5-Ene-4-thiazolidinones – An efficient tool in medicinal chemistry. European Journal of Medicinal Chemistry, 140, 542-594.
Kumar, R., Patil, S. (2017). Biological prospective of 4-thiazolidinone: a review. Hygeia:Journal for Drugs and Medicines, 9, 80-97.
Kryshchyshyn, A., Kaminskyy, D., Karpenko, O., Gzella, A., Grellier, P., & Lesyk, R. (2019).Thiazolidinone/thiazole based hybrids – New class of antitrypanosomal agents. European Journal of Medicinal Chemistry, 174, 292-308.
Liaras, K., Fesatidou, M., & Geronikaki, A. (2018). Thiazoles and Thiazolidinones as COX/LOX Inhibitors. Molecules, 23, 685-706.
Kaminskyy, D., Subtel'na, I., Zimenkovsky, B., Karpenko, O., Gzella, A., & Lesyk, R. (2015). Synthesis and evaluation of anticancer activity of 5-ylidene-4-aminothiazol-2(5H)-one derivatives. Journal of Medicinal Chemistry, 11, 517-530.
Сhulovska, Z., Chaban, T., Drapak, I., Matiychuk, V., Chaban, I., & Nektegaev, I. (2021). Synthesis of some С5 substituted 4-phenylimino-thiazolidin-2-ones as possible anti-inflammatory agents. Biointerface Research in Applied Chemistry, 11, 8009-8017.
Chaban, T., Ogurtsov, V., Chaban, I., Harkov, S., & Leluykh, M. (2019). Synthesis of some new 4-iminothiazolidine-2-ones as possible antioxidants agents. Pharmacia, 66, 27-32.
Badawya, M., Metwallya, N., & Okpya, D. (2015) Synthesis of some new 5-substituted-3-phenyl-4-thioxo-2-thiazolidinones and their fused thiopyrano[2,3-d]thiazole derivatives. Journal of Sulfur Chemistry, 36, 511-525.
Boominathan, R., Parimaladevi, B., Mandal, S., & Ghoshal, S. (2004). Anti-inflammatory evaluation of Ionidium suffruticosam Ging. in rats. Journal of Ethnopharmacology, 91, 367-370.
Panthong, A., Norkaew, P., Kanjanapothi, D., Taesotikul, T., Anantachoke, N., & Reutrakul, V. (2007). Anti-inflammatory, analgesic and antipyretic activities of the extract of gamboge from Garcinia hanburyi Hook. Journal of Ethnopharmacology, 111, 335-340.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Medical and Clinical Chemistry
This work is licensed under a Creative Commons Attribution 4.0 International License.
