Synthesis and radioligand-binding assay of 2,5-disubstituted thiadiazoles and evaluation of their anticonvulsant activities
Mahsa Toolabi
Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Search for more papers by this authorMona Khoramjouy
Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Search for more papers by this authorAyoub Aghcheli
Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorAdileh Ayati
Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorSetareh Moghimi
Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorLoghman Firoozpour
Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorSoraya Shahhosseini
Department of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Search for more papers by this authorAli Asadipour
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
Search for more papers by this authorKouros Divsalar
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
Search for more papers by this authorCorresponding Author
Mehrdad Faizi
Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Correspondence Mehrdad Faizi, Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, 1991953381 Tehran, Iran.
Email: [email protected]
Alireza Foroumadi, Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, 14174 Tehran, Iran.
Email: [email protected]
Search for more papers by this authorAlireza Foroumadi
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorMahsa Toolabi
Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Search for more papers by this authorMona Khoramjouy
Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Search for more papers by this authorAyoub Aghcheli
Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorAdileh Ayati
Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorSetareh Moghimi
Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorLoghman Firoozpour
Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorSoraya Shahhosseini
Department of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Search for more papers by this authorAli Asadipour
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
Search for more papers by this authorKouros Divsalar
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
Search for more papers by this authorCorresponding Author
Mehrdad Faizi
Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Correspondence Mehrdad Faizi, Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, 1991953381 Tehran, Iran.
Email: [email protected]
Alireza Foroumadi, Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, 14174 Tehran, Iran.
Email: [email protected]
Search for more papers by this authorAlireza Foroumadi
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorAbstract
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.
CONFLICTS OF INTERESTS
The authors declare that there are no conflicts of interest.
Supporting Information
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