Archive / Volume LXXVIII 2025

Vasyl ZHYLKO¹, Nataliia SLYVKA¹, Lesya SALIYEVA¹, Olga SHKURENKO¹, Ella KADYKALO¹, Tetyana BORTNIK², Andriy BORTNIK³, Mykhailo VOVK⁴

¹ Lesya Ukrainka Volyn National University, Voli Ave., 13, 43025 Lutsk, Ukraine
e-mail: slivka.natalia@vnu.edu.ua

² Polissya Research Station of the National Scientific Center "O.N. Sokolovsky Institute of Soil Science and Agrochemistry", Shevchenko St., 35, 43000 Lutsk, Ukraine

³ Northwestern Interregional Center of the State Institution "Institute of Soil Protection of Ukraine", Hlushets St., 49, 43010 Lutsk, Ukraine

⁴ Institute of Organic Chemistry of the NAS of Ukraine Academician Kukhariya St., 5, 02660 Kyiv, Ukraine

ANALYSIS OF PHYTOHORMONAL ACTIVITY OF 2-(2-OXOINDOLIN-3-YLIDENE)-SUPTITUTED DERIVATIVES OF IMIDAZOTHIAZOLE AND THIAZOLOPYRIMIDENE

The first synthesized 2-(2-oxoindoline-3-ylidene)-substituted 5,6-dihydroimidazo[2,1-b]thiazolones and 6,7-dihydrothiazolo[3,2-a]pyrimidinones were investigated to assess their effect on physiological and biochemical processes in the plant organism Cucumis sativus at the initial stages of organogenesis. The experimental results indicate the diverse biological activity of these compounds on growth processes and general plant development. Compounds 4a and 5b, which contain a methyl group in their structure as part of the 2-oxoindoline-3-ylidene fragment in imidazo[2,1-b]thiazol-3(2H)-one and thiazolo[3,2-a]pyrimidin-3(5H)-one, respectively, demonstrated a pronounced inhibitory effect. The effect of inhibiting growth processes depended on the concentration, demonstrating a pattern: with a decrease in concentration, a weakening of the inhibitory effect was observed, but its complete leveling did not occur. Compound 5a 2-(2-oxoindoline-3-ylidene)-6,7-dihydro-2H-thiazolo[3,2-a]pyrimidin-3(5H)-one – showed an ambivalent effect: at a concentration of 0.1%, growth inhibition was observed, while at lower concentrations (0.01–0.0001%), stimulation of seedling development was observed. No statistically significant effect on biometric parameters was found for compounds 4b, 4c, and 5c. However, at a concentration of 0.1%, a weak inhibitory tendency was observed, while at 0.01–0.0001 %, a weak stimulation of growth processes was noted. Of particular interest is compound 5c, which contains an NO₂ group in the 2-oxoindoline-3-ylidene fragment of the thiazolopyrimidine nucleus. It caused a noticeable increase in the length of seedlings, indicating a possible activation of elongation growth, characteristic of gibberellin-type phytohormones. Among all the studied compounds, the most pronounced stimulating activity was shown by compound 4d 2-(5-nitro-2-oxoindoline-3-ylidene)-5,6-dihydroimidazo[2,1-b]thiazol-3(2H)-one. Its effectiveness showed a clear concentration dependence, with the best results obtained when using a solution with a concentration of 0.0001 %, where a statistically significant increase in seedling mass and length was recorded compared to the control.
The results indicate these compounds' potential ability to influence the regulation of growth processes at the early stages of development, which is a prerequisite for the formation of viable and stress-resistant plants.

Keywords: imidazothiazolones; thiazolopyrimidines; growth-regulatory activity; inhibitors; plant growth stimulants.

References:

1. Keshari M., Khan R.A., Habibullah Yusuf, M., Ahmed B. Pharmacophore modeling, design, and synthesis of potent antihypertensives, oxazolo/thiazolo-[3,2-a]-pyrimidin-3(2H)-one, and 1,5-dihydroimidazo-[1,2-a]-pyrimidin-3(2H)-one derivatives: A pilot trial. Bioorg. Med. Chem. Lett. 2020. Vol. 30(23). P. 127604. (https://doi.org/10.1016/j.bmcl.2020.127604).
2. Jin C.-H., Jun K.-Y., Lee E., Kim S., Kwon Y., Kim K., Na Y. Ethyl 2-(benzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate analogues as a new scaffold for protein kinase casein kinase 2 inhibitor. Bioorg. Med. Chem. 2014. Vol. 22(17). P. 4553–4565. http://dx.doi.org/10.1016/j.bmc.2014.07.037. 3. Brough P.A., Cheetham S.C., Kerrigan F., Watts J.P. Thiazoloderivatives and pharmaceutical compositions containing them. WO Patent 00/71549. 2000. 4. Aretz J., Anumala U.R., Fuchsberger F.F., Molavi N., Ziebart N., Zhang H., Marc Nazaré Rademacher C. Allosteric inhibition of a mammalian lectin. J. Am. Chem. Soc. 2018. Vol. 140(44). P. 14915–14925. https://doi.org/10.1021/jacs.8b08644. 5. Tozkoparan B., Ertan M., Kelicen P., Demirdamar R. Synthesis and anti-inflammatory activities of some thiazolo[3,2-a]pyrimidine derivatives. Il Farmaco 1999. Vol. 54. P. 588–593. https://doi.org/10.1016/S0014-827X(99)00068-3. 6. Batool I., Saeed A., Qureshi I.Z., Kalsoom S., Razzaq A. Synthesis, molecular docking and biological evaluation of new thiazolopyrimidine carboxylates as potential antidiabetic and antibacterial agents. Res Chem Intermed. 2016. Vol. 42. P. 1139–1163. https://doi.org/10.1007/s11164-015-2078-2. 7. Al-Rashood S.T., Elshahawy S.S., El-Qaias A.M., El-Behedy D.S., Hassanin A.A., El-Sayed S.M., El-Messery S.M., Shaldam M.A., Hassan G.S. New Thiazolopyrimidine as anticancer agents: Synthesis, biological evaluation, DNA binding, Molecular modeling and ADMET study. Bioorg. Med. Chem. Lett. 2020. Vol. 30(23). P. 127611. https://doi.org/10.1016/j.bmcl.2020.127611. 8. El-Borai M. A., Rizk H. F., Ibrahim S. A., El-Sayed H. F. Microwave Assisted Synthesis of Fused Thiazoles in Multicomponent System and Theirin in vitro Antitumor, Antioxidant, and Antimicrobial Activities. J. Heterocyclic Chem. 2017. Vol. 54(2). P. 1031–1041. https://doi.org/10.1002/jhet.2671. 9. Hassan G.S. Synthesis and antitumor activity of certain new thiazolo[2,3-b]quinazoline and thiazolo[3,2-a]pyrimidine analogs. Med. Chem. Res. 2014. Vol. 23. P. 388–401. https://doi.org/10.1007/s00044-013-0649-6. 10. Goyal A., Kaur B., Kaur A., Gupta V.K., Gupta M. Synthesis and biological activity of 2-(4-substituted benzylidene)-7-methyl-2H-thiazolo[3,2-a]pyrimidine-3,5-diones. Bull. Faculty Pharm. Cairo Univ. 2014. Vol. 52(2). P. 259–267. http://dx.doi.org/10.1007/BF02980237. 11. Devineni, S.R., Madduri, T.R., Chamarthi, N.R. et al. An efficient microwave-promoted three-component synthesis of thiazolo[3,2-a]pyrimidines catalyzed by SiO2–ZnBr2 and antimicrobial activity evaluation. Chem. Heterocycl. Comp. 2019. Vol. 55. P. 266–274. https://doi.org/10.1007/s10593-019-02452-2. 12. Abdel Moty S.G., Hussein M.A., Abdel Aziz S.A., Abou-Salim M.A. Design and synthesis of some substituted thiazolo[3,2-a]pyrimidine derivatives of potential biological activities. Saudi Pharm. J. 2016. Vol. 24. P. 119–132. https://doi.org/10.1016/j.jsps.2013.12.016. 13. Danel K. Pedersen E.B., Nielsen C. Synthesis and Anti-HIV-1 Activity of Novel 2,3-Dihydro-7H-thiazolo[3,2-a]pyrimidin-7-ones. J. Med. Chem. 1998. Vol. 41. P. 191–198. https://doi.org/10.1021/jm970443m. 14. Haga T., Nagano H., Enomoto M., Morita K., Sato M. Preparation of isatin derivatives as herbicides. Jpn. Patent 63313770. 1988. 15. Wang J., Tan H., Li Y., Ma Y., Li Z., Guddat L.W. Chemical Synthesis, in Vitro Acetohydroxyacid Synthase (AHAS) Inhibition, Herbicidal Activity, and Computational Studies of Isatin Derivatives. J. Agric. Food Chem., 2011. Vol. 59(18). P. 9892–9900. https://doi.org/10.3390/molecules29112409. 16. Tan H.Z., Wang W.M., Shang J.L., Song H.B., Li Z.M., Wang J.G. Syntheses, crystal structures and bioactivities of two isatin derivatives. Chinese J. Struct. Chem. 2011. Vol. 30(4). P. 502–507. 17. Schreiber K., Stephan U., Wegner G. Agent for controlling the growth of clover, especially red clover. Ger. Patent DD121011. 1976. 18. Slyvka N.Yu., Saliyeva L.M., Zhylko V.I., Tkachuk V.M., Vovk M.V. Synthesis and antioxidant activity of new 2-(2-oxoindoline-3-ylydene) substituted 5,6-dihydroimidazo [2,1-b]thiazolones and 6,7-dihydro-thiazolo[3,2-a]pyrimidinones. Voprosy khimii i khimicheskoi tekhnologii. 2025. Vol. 1. P. 71–79. (in Ukrainian). https://doi.org/10.32434/0321-4095-2025-158-1-71-79. 19. Zhylko V., Slyvka N, Saliyeva L., Shkurenko О., Kadykalo Е., Bortnik Т., Vovk М. Growth inhibiting activity of 2-(2-oxoindoline-3-ylidene) substituted 5,6-dihydroimidazo[2,1-b]-thiazolones and 6,7-dihydrothiazolo[3,2-a]pyrimidinones. Problems of Chemistry and Sustainable Development. 2025. Vol. 1. P. 10–18. (in Ukrainian). https://doi.org/10.32782/pcsd-2025-1-2.