Synthesis and Radioligand-Binding Assay of 2,5-Disubstituted Thiadiazoles and Evaluation of Their Anticonvulsant Activities

Synthesis and Radioligand-Binding Assay of 2,5-Disubstituted Thiadiazoles and Evaluation of Their Anticonvulsant Activities Publisher Pubmed

Toolabi M¹ ; Khoramjouy M² ; Aghcheli A³ ; Ayati A³ ; Moghimi S³ ; Firoozpour L³ ; Shahhosseini S⁴ ; Shojaei R⁵ ; Asadipour A⁶ ; Divsalar K⁶ ; Faizi M² ; Foroumadi A^{6, 7}

Show Affiliations

1. Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2. Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
4. Department of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5. Parsian Pharmaceutical Co., Alborz, Iran
6. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
7. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Archiv der Pharmazie Published:2020

Abstract

In this study, a number of 2,5-disubstituted 1,3,4-thiadiazoles were synthesized using an appropriate synthetic route, and their anticonvulsant activity was determined by the maximal electroshock seizure (MES) test and their neurotoxicity was evaluated by the rotarod test. Additionally, their hypnotic activity was tested using the pentobarbital-induced sleep test. Compounds 7 (ED50 = 1.14 and 2.72 μmol/kg in the MES and sleep tests, respectively) and 11 (ED50 = 0.65 and 2.70 μmol/kg in the MES and sleep tests, respectively) were the most potent ones in the sleep test and anticonvulsant test, showing a comparable activity with diazepam as the reference drug. The results of in vivo studies, especially the antagonistic effects of flumazenil, and also the radioligand-binding assay confirmed the involvement of benzodiazepine (BZD) receptors in the anticonvulsant and hypnotic activity of compounds 7 and 11. Finally, the docking study of compound 11 in the BZD-binding site of the GABAA (gamma-aminobutyric acid) receptor confirmed the possible binding of the compound to the BZD receptors. We concluded that the novel 1,3,4-thiadiazole derivatives with appropriate substitution at positions 2 and 5 of the heterocyclic ring had a good affinity to BZD receptors and showed significant efficacy in the pharmacological tests. © 2020 Deutsche Pharmazeutische Gesellschaft

Style	Citing Format
MLA	Toolabi M, et al.. "Synthesis and Radioligand-Binding Assay of 2,5-Disubstituted Thiadiazoles and Evaluation of Their Anticonvulsant Activities." Archiv der Pharmazie, vol. 353, no. 12, 2020, pp. -.
APA	Toolabi M, Khoramjouy M, Aghcheli A, Ayati A, Moghimi S, Firoozpour L, Shahhosseini S, Shojaei R, Asadipour A, Divsalar K, Faizi M, Foroumadi A (2020). Synthesis and Radioligand-Binding Assay of 2,5-Disubstituted Thiadiazoles and Evaluation of Their Anticonvulsant Activities. Archiv der Pharmazie, 353(12), -.
Chicago	Toolabi M, Khoramjouy M, Aghcheli A, Ayati A, Moghimi S, Firoozpour L, Shahhosseini S, et al.. "Synthesis and Radioligand-Binding Assay of 2,5-Disubstituted Thiadiazoles and Evaluation of Their Anticonvulsant Activities." Archiv der Pharmazie 353, no. 12 (2020): -.
Harvard	Toolabi M et al. (2020) 'Synthesis and Radioligand-Binding Assay of 2,5-Disubstituted Thiadiazoles and Evaluation of Their Anticonvulsant Activities', Archiv der Pharmazie, 353(12), pp. -.
Vancouver	Toolabi M, Khoramjouy M, Aghcheli A, Ayati A, Moghimi S, Firoozpour L, et al.. Synthesis and Radioligand-Binding Assay of 2,5-Disubstituted Thiadiazoles and Evaluation of Their Anticonvulsant Activities. Archiv der Pharmazie. 2020;353(12):-.
BibTex	@article{ author = {Toolabi M and Khoramjouy M and Aghcheli A and Ayati A and Moghimi S and Firoozpour L and Shahhosseini S and Shojaei R and Asadipour A and Divsalar K and Faizi M and Foroumadi A}, title = {Synthesis and Radioligand-Binding Assay of 2,5-Disubstituted Thiadiazoles and Evaluation of Their Anticonvulsant Activities}, journal = {Archiv der Pharmazie}, volume = {353}, number = {12}, pages = {-}, year = {2020} }
RIS	TY - JOUR AU - Toolabi M AU - Khoramjouy M AU - Aghcheli A AU - Ayati A AU - Moghimi S AU - Firoozpour L AU - Shahhosseini S AU - Shojaei R AU - Asadipour A AU - Divsalar K AU - Faizi M AU - Foroumadi A TI - Synthesis and Radioligand-Binding Assay of 2,5-Disubstituted Thiadiazoles and Evaluation of Their Anticonvulsant Activities JO - Archiv der Pharmazie VL - 353 IS - 12 SP - EP - PY - 2020 ER -

Science Communicator Platform

Authors

Authors Affiliations

Abstract