Generic placeholder image

Central Nervous System Agents in Medicinal Chemistry


ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

Research Article

Design, Synthesis and Biological Activity of Some 4, 5-Disubstituted-2, 4- Dihydro-3H-1, 2, 4- Triazole-3-Thione Derivatives

Author(s): Krishan Kumar Verma*, Umesh Kumar Singh and Jainendra Jain

Volume 19, Issue 3, 2019

Page: [197 - 205] Pages: 9

DOI: 10.2174/1871524919666190722144424


Background: In the present study, 4, 5-disubstituted triazol-3-thione derivatives were synthesized and evaluated for anticonvulsant activity along with neurotoxicity determination.

Materials and Methods: The synthesized compounds were characterized using FTIR, 1H-NMR and MS. The anticonvulsant activity was assessed by Maximal Electroshock (MES) test and subcutaneous Pentylenetetrazole (scPTZ) tests and neurotoxicity was assessed by rotarod test. Docking was also performed to study the interactions of compounds with LYS329 residue of gamma amino butyric acid aminotransferase (GABA-AT) using Autodock 4.2 software.

Results: The compounds 7a and 9a with significant pharmacological activity were also found to interact with LYS329 residue of GABA-AT by H-bond with a docking score of -5.92 kcal/mol (Ki = 41.99 μM) and -5.87 kcal/mol (Ki = 49.83 μM) respectively.

Conclusion: Most of the compounds were found to be active in MES test but only seven showed protection in scPTZ test.

Keywords: Triazol-3-thiones, anticonvulsant, scPTZ, MES, docking, GABA-AT.

Graphical Abstract
William, F. Foye’s Principles of Medicinal Chemistry. 1996.
Ko, D.Y. Epilepsy & Seizures., Available at;
Chang, B.S.; Lowenstein, D.H. Epilepsy. N. Engl. J. Med., 2003, 349(13), 1257-1266.
[] [PMID: 14507951]
Yogeeswari, P.; Ragavendran, J.V.; Thirumurugan, R.; Saxena, A.; Sriram, D. Ion channels as important targets for antiepileptic drug design. Curr. Drug Targets, 2004, 5(7), 589-602.
[] [PMID: 15473249]
Löscher, W. New visions in the pharmacology of anticonvulsion. Eur. J. Pharmacol., 1998, 342(1), 1-13.
[] [PMID: 9544786]
Perucca, E. The new generation of antiepileptic drugs: advantages and disadvantages. Br. J. Clin. Pharmacol., 1996, 42(5), 531-543.
[] [PMID: 8951184]
Lin, Z.; Kadaba, P.K. Molecular targets for the rational design of antiepileptic drugs and related neuroprotective agents. Med. Res. Rev., 1997, 17(6), 537-572.
[<537:AID-MED3>3.0.CO;2-2] [PMID: 9359082]
Sinha, R.; Sara, U.V.S.; Khosa, R.L.; Stables, J.; Jain, J. Nicotinic acid hydrazones: A novel anticonvulsant pharmacophore. Med. Chem. Res., 2011, 20, 1499-1504.
Küçükgüzel, S.G.; Çıkla-Süzgün, P. Recent advances bioactive 1,2,4-triazole-3-thiones. Eur. J. Med. Chem., 2015, 97, 830-870.
[] [PMID: 25563511]
Plech, T.; Kaproń, B.; Luszczki, J.J.; Paneth, A.; Siwek, A.; Kołaczkowski, M.; Żołnierek, M.; Nowak, G. Studies on the anticonvulsant activity of 4-alkyl-1,2,4-triazole-3-thiones and their effect on GABAergic system. Eur. J. Med. Chem., 2014, 86, 690-699.
[] [PMID: 25226229]
Plech, T.; Luszczki, J.J.; Wujec, M.; Flieger, J.; Pizoń, M. Synthesis, characterization and preliminary anticonvulsant evaluation of some 4-alkyl-1,2,4-triazoles. Eur. J. Med. Chem., 2013, 60, 208-215.
[] [PMID: 23291122]
Yadav, M.K.; Tripathi, L.; Goswami, D. Synthesis and anticonvulsant activity (Chemo-Shock) of some novel schiff bases of substituted 4-amino-5-phenyl-2, 4-dihydro-[1, 2, 4]-triazole-3-thione. Saudi J. Med. Pharm. Sci., 2017, 3(1), 45-54.
Siddiqui, N.; Alam, M.S.; Ahsan, W. Synthesis, anticonvulsant and toxicity evaluation of 2-(1H-indol-3-yl)acetyl-N-(substituted phenyl)hydrazine carbothioamides and their related heterocyclic derivatives. Acta Pharm., 2008, 58(4), 445-454.
[] [PMID: 19103578]
Parmar, K.; Prajapati, S.; Patel, R. A simple and efficient procedure for synthesis of biologically active 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole -2-aryl-thiazolidine-4-one derivatives. Res. J. Chem. Sci, 2011, 1(1), 18-24.
Plech, T.; Kaproń, B.; Luszczki, J.J.; Wujec, M.; Paneth, A.; Siwek, A.; Kołaczkowski, M.; Zołnierek, M.; Nowak, G. Studies on the anticonvulsant activity and influence on GABA-ergic neurotransmission of 1,2,4-triazole-3-thione- based compounds. Molecules, 2014, 19(8), 11279-11299.
[] [PMID: 25090118]
Porter, R.J.; Cereghino, J.J.; Gladding, G.D.; Hessie, B.J.; Kupferberg, H.J.; Scoville, B.; White, B.G. Antiepileptic drug development program. Cleve. Clin. Q., 1984, 51(2), 293-305.
[] [PMID: 6380818]
Storici, P.; De Biase, D.; Bossa, F.; Bruno, S.; Mozzarelli, A.; Peneff, C.; Silverman, R.B.; Schirmer, T. Structures of Gamma-Aminobutyric Acid (GABA) aminotransferase, a pyridoxal 5′-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin. J. Biol. Chem., 2004, 279(1), 363-373.
[] [PMID: 14534310]

© 2024 Bentham Science Publishers | Privacy Policy