Screening study of new thiazolidinone derivatives for anticonvulsant activity




antiepileptic drugs, epilepsy, thiazolidinone derivatives



The search for new antiepileptic drugs that would have greater margins of safety and fewer adverse effects is relevant. Thiazolidinone are a promising class for the development of new anticonvulsants.

Aim. To conduct a screening study of new thiazolidinone derivatives for anticonvulsant activity on a seizure model induced by pentylenetetrazole and maximal electroshock; to analyze the structure – activity relationship; to reveal a lead-compound and investigate its dose-dependent manner.

Materials and methods. Basic screening seizure models of pentylenetetrazol and maximal electroshock test were used in mice. The test original 9 thiazolidinone derivatives (100 mg/kg) and the reference drugs of sodium valproate (300 mg/kg), carbamazepine (40 mg/kg) were administered intragastrically 30 minutes before subcutaneous administration of pentylenetetrazol (90 mg/kg) or induction with maximal electroshock by giving a current with strength of 50 mA and frequency of 50 Hz for 0.2 s. In order to study the dose-dependent manner, the lead-compound was administered intragastrically in doses ranging from 25 mg/kg to 150 mg/kg.

Results. A total of 9 compounds were studied, of which 3 did not affect experimental convulsions, 2 showed proconvulsive activity, and 4 had an anticonvulsant effect. The lead-compound 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone was determined under laboratory code Les-6222, which exhibited the highest anticonvulsant properties. The “structure–anticonvulsant activity” relationship in a series of thiazolidinone derivatives was analyzed. The dose-dependent manner of 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone anticonvulsant effect was studied using 2 seizure models, and the most effective dose of 100 mg / kg was identified.

Conclusions. 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylamino)-4-thiazolidinone is a promising compound for in-depth studies on anticonvulsant and related pharmacological activities in order to develop new original anticonvulsants.


Espinosa-Jovel, C., Toledano, R., Aledo-Serrano, Á., García-Morales, I., & Gil-Nagel, A. (2018). Epidemiological profile of epilepsy in low income populations. Seizure, 56, 67-72.

Chen, Z., Brodie, M. J., Liew, D., & Kwan, P. (2018). Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study. JAMA Neurology, 75(3), 279-286.

Bigelow, M. D., & Kouzani, A. Z. (2019). Neural stimulation systems for the control of refractory epilepsy: a review. Journal of NeuroEngineering and Rehabilitation, 16(1), Article 126.

Nikalje, A. P., Ansari, A., Bari, S., & Ugale, V. (2015). Synthesis, Biological Activity, and Docking Study of Novel Isatin Coupled Thiazolidin-4-one Derivatives as Anticonvulsants. Archiv Der Pharmazie, 348(6), 433-445.

Jangam, S. S., Wankhede, S. B., & Chitlange, S. S. (2018). Molecular docking, synthesis and anticonvulsant activity of some novel 3-(2-substituted)-4-oxothiazolidine-3-yl)-2-phenylquinazoline-4(3H)-ones. Research on Chemical Intermediates, 45(2), 471-486.

Archana, & Saini, S. (2018). Synthesis and evaluation of some newerthiazolidinonyl substituted quinazolinones as potent anticonvulsant agents. International Journal of ChemTech Research, 11(11), 09-16.

Faizia, M., Jahania, R., Ebadib, S. A., Tabatabaic, S. A., Rezaeec, E., Lotfalieic, M., Aminid, M., & Almasiradb, A. (2017). Novel 4-thiazolidinone derivatives as agonists of benzodiazepine receptors: design, synthesis and pharmacological evaluation. EXCLI Journal, 16, 52-62.

Kaur Manjal, S., Kaur, R., Bhatia, R., Kumar, K., Singh, V., Shankar, R., Kaur, R., & Rawal, R. K. (2017). Synthetic and medicinal perspective of thiazolidinones: A review. Bioorganic Chemistry, 75, 406-423.

Pandey, A. K. (2019). Anticonvulsant activity of novel Schiff bases of thiadiazole derivatives. Bangladesh Journal of Pharmacology, 14(3), 127-128.

Myronenko, S. I., Pinyazhko, О. R., & Lesyk, R. B. (2015). Skryninh spoluk z protysudomnoiu aktyvnistiu sered pokhidnykh 4-tiazolidynonu [Screening of compounds with anticonvulsant activity among 4-thiazolidinone derivatives]. Farmakolohiia ta likarska toksykolohiia, (4-5), 33-38. [in Ukrainian].

Mishchenko, M. V., Shtrygol, S. Yu., Lesyk, R. B., & Kaminskyi, D. V. (2019). Tiazolzamishcheni pokhidni 2,4-tiazolidyndionu, shcho vyiavliaiut antykonvulsantnu diiu [Thiazole-substituted 2,4-thiazolidinedione derivatives exhibiting anticonvulsant activity] (Ukraine. Patent No. 137726). Ukraina. Derzhavna sluzhba intelektualnoi vlasnosti Ukrainy. [in Ukrainian].

Myronenko, S. I., Kaminskyy, D. V., Nektegayev, I. O., Pinyazko, O. R., & Lesyk, R. B. (2012). Poshuk novykh antykonvulsantnykh ahentiv v riadu 4-tiazolidynoniv ta sporidnenykh heterotsyklichnykh system [Search of new anticonvulsant agents among 4-thiazolidinones and related heterocyclic systems]. Klinichna farmatsiia, farmakoterapiia ta medychna standartyzatsiia, (1-2), 124-131. [in Ukrainian].

Hock, F. J. (Ed.). (2016). Drug Discovery and Evaluation: Pharmacological Assays. Springer, Cham.

Mironov, A. N., Bunyatyan, N. D., Vasil'ev, A. N., Verstakova, O. L., Zhuravleva, M. V., Lepakhin, V. K., Korobov, N. V., Merkulov, V. A., Orekhov, S. N., Sakaeva, I. V., Uteshev, D. B., & Yavorskii, A. N. (Eds.). (2012). Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv. Chast' pervaya [Guidelines for conducting preclinical studies of drugs. Part one]. ZAO «Grif i K». [in Russian].

How to Cite

Mishchenko MV, Shtrygol SY, Lesyk RB, Lozynskyi AV, Holota SM. Screening study of new thiazolidinone derivatives for anticonvulsant activity. Zaporozhye Medical Journal [Internet]. 2020Dec.9 [cited 2024May20];22(6). Available from:



Original research