5-Sulfurofunctionalized (1,3-thiazolidin-2-ylidene)pyrimidine-2,4,6-triones and their antibacterial activity

Authors

  • M. V. Litvinchuk Lesya Ukrainka East European National University, Ukraine
  • A. V. Bentya Institute of Organic Chemistry of the NAS of Ukraine, Ukraine
  • A. M. Grozav Bukovinian State Medical University, Ukraine
  • N. D. Yakovychuk Bukovinian State Medical University, Ukraine
  • N. Yu. Slyvka Lesya Ukrainka East European National University, Ukraine
  • M. V. Vovk Institute of Organic Chemistry of the NAS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.18.943

Keywords:

5-sulfurofunctionalized 1, 3-thiazolidines, derivatives of barbituric acid, antibacterial activity

Abstract

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.

 

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References

  1. 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
  2. Fischer, E., von Mering, J. (1903). Ueber eine neue Klasse von Schlafmitteln. Therapie der Gegenwart, 44, 97–101.
  3. 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
  4. 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
  5. 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
  6. 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.
  7. intimp.2016.06.004
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. Chiou, G. (1993). The use of OB–104 to treat inflammation. Pat. WO9310789; declared 03.12.1991; published 10.06.1993.
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. Watanabe, T. (2010). Compound for photoresist, photoresist liquid, and etching method using the same. Pat. US20100104985; declared: 05.03.2008; published: 29.04.2010.
  25. 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.
  26. Litvinchuk, М. B., Bentia, А. V., Slyvka, N. Yu., Vovk, М. V. (2017). Ukrainskyi Khimichnyi Zhurnal, 83 (10), 90–99.
  27. Metodychni vkazivky 9.9.5–143–2007 (2007). Vyznachennia chutlyvosti mikroorganizmiv do antybakterialnykh reparative. Kyiv: MOZ Ukrainy, 63.

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Published

2018-09-19

How to Cite

(1)
Litvinchuk, M. V.; Bentya, A. V.; Grozav, A. M.; Yakovychuk, N. D.; Slyvka, N. Y.; Vovk, M. V. 5-Sulfurofunctionalized (1,3-Thiazolidin-2-ylidene)pyrimidine-2,4,6-Triones and Their Antibacterial Activity. J. Org. Pharm. Chem. 2018, 16, 39-44.

Issue

Vol. 16 No. 3(63) (2018)

Section

Original Researches

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