5-Sulfurofunctionalized (1,3-thiazolidin-2-ylidene)pyrimidine-2,4,6-triones and their antibacterial activity
Keywords:5-sulfurofunctionalized 1, 3-thiazolidines, derivatives of barbituric acid, antibacterial activity
Aim. Studying of the antimicrobial and antifungal activity of 5-sulfurofunctionalized derivatives (1,3-thiazolidine-2-ylidene)pyrimidine-2,4,6(1H,3H,5H)-triones, obtained by the interaction of [5-(iodomethyl)thiazolidine-2-ylidene]pyrimidine-2,4,6(1H,3H,5H)-triones with a number of S-nucleophilic reagents.
Results and discussion. A series of new derivatives containing 5-thiocyanato(acetylthio, butylxanthonato)methyl groups has been synthesized by functionalization of [5-(iodomethyl)thiazolidine-2-ylidene]pyrimidine-2,4,6(1H,3H,5H)-triones with sulfur-containing reagents. Among the synthesized compounds substances with moderate antibacterial and antifungal activity were found.
Experimental part. Novel 5-thiofunctionalized derivatives were obtained by reaction of [5-(iodomethyl)thiazolidine-2-ylidene]pyrimidine-2,4,6(1H,3H,5H)-triones with potassium thiocyanate, potassium thioacetate in dimethylformamide or potassium buthylxanthate in ethanol with 72-99% yields. The structure of new compounds was confirmed by complex spectral methods. Screening of the antifungal and antimicrobial effects of the synthesized compounds was carried out using a micro-method of double serial dilutions in a liquid nutrient medium.
Conclusions. 5-Sulfurofunctionalized (1,3-thiazolidine-2-ylidene)pyrimidine-2,4,6-triones, obtained by the reaction of corresponding 5-iodomethyl derivatives with a number of S-nucleophilic reagents, have shown moderate antimicrobial and antifungal activity and are promising for further in-depth research.
- Ernst, B., Clark, G., Grundmann, O. (2015). The Physicochemical and Pharmacokinetic Relationships of Barbiturates – From the Past to the Future. Current Pharmaceutical Design, 21 (25), 3681–3691. doi: 10.2174/1381612821666150331131009
- Fischer, E., von Mering, J. (1903). Ueber eine neue Klasse von Schlafmitteln. Therapie der Gegenwart, 44, 97–101.
- Ding, K., Zhou, Z., Zhou, S., Yuan, Y., Kim, K., Zhang, T., Zhan, C.–G. (2018). Design, synthesis, and discovery of 5–((1,3–diphenyl–1 H –pyrazol–4–yl) methylene)pyrimidine–2,4,6(1 H ,3 H ,5 H )–triones and related derivatives as novel inhibitors of mPGES–1. Bioorganic & Medicinal Chemistry Letters, 28(5), 858–862. doi: 10.1016/j.bmcl.2018.02.011
- Dixit, V. A., Rathi, P. C., Bhagat, S., Gohlke, H., Petersen, R. K., Kristiansen, K., Chakraborti, A. K., Bharatam, P. V. (2016). Design and synthesis of novel Y–shaped barbituric acid derivatives as PPARγ activators. European Journal of Medicinal Chemistry, 108, 423–435. doi: 10.1016/j.ejmech.2015.11.030
- Penthala, N. R., Ketkar, A., Sekhar, K. R., Freeman, M. L., Eoff, R. L., Balusu, R., Crooks, P. A. (2015). 1–Benzyl–2–methyl–3–indolylmethylene barbituric acid derivatives: Anti–cancer agents that target nucleophosmin 1 (NPM1). Bioorganic & Medicinal Chemistry, 23 (22), 7226–7233. doi: 10.1016/j.bmc.2015.10.019
- Xu, C., Wyman, A. R., Alaamery, M. A., Argueta, S. A., Ivey, F. D., Meyers, J. A., Lerner, A., Burdo, T. H., Connolly, T., Hoffman, C. S., Chiles, T. C. (2016). Anti–inflammatory effects of novel barbituric acid derivatives in T lymphocytes. International Immunopharmacology, 38, 223–232. doi: 10.1016/j.
- Jain, A. K., Vaidya, A., Ravichandran, V., Kashaw, S. K., Agrawal, R. K. (2012). Recent developments and biological activities of thiazolidinone derivatives: A review. Bioorg Bioorganic & Medicinal Chemistry, 20 (11), 3378–3395. doi: 10.1016/j.bmc.2012.03.069
- Tripathi, A. C., Gupta, S. J., Fatima, G. N., Sonar, P. K., Verma, A., Saraf, S.K. (2014). 4–Thiazolidinones: The advances continue… European Journal of Medicinal Chemistry, 72, 52–77. doi: 10.1016/j.ejmech.2013.11.017
- Belluco, P., Gaion, R. M., Maragno, I., Dorigo, P. (1990). Etozoline and vascular spasm. Pharmacological Research, 22,123–124. doi: 10.1016/S1043–6618(09)80059–5
- Salem, M. A. (2017). Synthesis of New Thiazole, Bithiazolidinone and Pyrano[2,3–d]thiazole Derivatives as Potential Antimicrobial Agents. Croatica Chemica Acta, 90 (1), 7–15. doi: 10.5562/cca2955
- Hanna, M. M., George, R. F. (2013). ChemInform Abstract: Facile Synthesis and Quantitative Structure–Activity Relationship Study of Antitumor Active 2–(4–Oxo–thiazolidin–2–ylidene)–3–oxo–propionitriles. ChemInform, 44 (7). doi: 10.1002/chin.201307111
- Helal, M. H. M., Salem, M. A., El–Gaby, M. S. A., Aljahdali, M. (2013). Synthesis and biological evaluation of some novel thiazole compounds as potential anti–inflammatory agents. European Journal of Medicinal Chemistry, 65, 517–526. doi: 10.1016/j.ejmech.2013.04.005
- Chiou, G. (1993). The use of OB–104 to treat inflammation. Pat. WO9310789; declared 03.12.1991; published 10.06.1993.
- Fischer, W., Bodewei, R., Satzinger, G. (1992). Anticonvulsant and sodium channel blocking effects of ralitoline in different screening models. Naunyn–Schmiedeberg’s Arch Pharmacology, 346 (4), 442–452. doi: 10.1007/bf00171088
- Zeng, F., Liu, P., Shao, X., Liab, Z., Xu, X. (2016). Catalyst–free and selective synthesis of 2–aminothiophenes and 2–amino–4,5–dihydrothiophenes from 4–thiazolidinones in water. Royal Society of Chemistry Advances, 6 (64), 59808–59815. doi: 10.1039/C6RA11151C
- Sogame, S., Suenaga, Y., Atobe, M., Kawanishi, M., Tanaka, E., Miyoshi, S. (2014). Discovery of a benzimidazole series of ADAMTS–5 (aggrecanase 2) inhibitors by scaffold hopping. European Journal of Medicinal Chemistry, 71, 250–258. doi: 10.1016/j.ejmech.2013.10.075
- Atobe, M., Maekawara, N., Ishiguro, N., Sogame, S., Suenaga, Y., Kawanishi, M., Suzuki, H., Jinno, N., Tanaka, E., Miyoshi, S. (2013). A series of thiazole derivatives bearing thiazolidin–4–one as non–competitive ADAMTS–5 (Aggrecanase–2) inhibitors. Bioorganic & Medicinal Chemistry Letters, 23 (7), 2106–2110. doi: 10.1016/j.bmcl.2013.01.121
- Schwede, W., Schulze, V., Buchmann, B., Briem, H., Siemeister, G., Boemer, U., Parczyk, K. (2006). Thiazolidinones and the use therof as polo–like kinase inhibitors. Pat. US2006079503; declared 29.04.2003; published 13.04.2006.
- Takagi, M. (2004). Oxa(thia)zolidine compounds, proxess for preparation thereof and anti–inflammatory agents. Pat. EP1410822; declared: 25.06.2001; published: 21.04.2004.
- Shimohara, N., Nagase, H., Tsujihata, S. (2008). Polymerizable compound, polymer, ink composition, printed articles and inkjet recording method. Pat. US20080241416; declared: 20.03.2008; published: 02.10.2008.
- Tsuchimura, T. (2006). Ink composition, ink jet recording, method, printed material method of producing planographic printing plate, and planographic printing plate. Pat. US2006182937; declared: 22.12.2005; published: 17.08.2006.
- Hanaki, N., Motoki, M., Yawata, T. (2010). Heterocyclic compound, ultraviolet absorbent and composition containing the same: Pat. US 20100210762; declared: 15.08.2008; published: 19.08.2010.
- Watanabe, T. (2010). Compound for photoresist, photoresist liquid, and etching method using the same. Pat. US20100104985; declared: 05.03.2008; published: 29.04.2010.
- Wolleb, H., Wolleb, A., Bienewald, F., Schmidhalter, B., Budry, J. L., Spahni, H. (2007). Optical recording matherials writable using blue lasers. Pat. US 20070172624; declared: 16.02.2005; published: 26.07.2007.
- Litvinchuk, М. B., Bentia, А. V., Slyvka, N. Yu., Vovk, М. V. (2017). Ukrainskyi Khimichnyi Zhurnal, 83 (10), 90–99.
- Metodychni vkazivky 9.9.5–143–2007 (2007). Vyznachennia chutlyvosti mikroorganizmiv do antybakterialnykh reparative. Kyiv: MOZ Ukrainy, 63.
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