Synthesis, structure elucidation and cytotoxic activities of 2,5-disubstituted-1,3,4-thiadiazole and l,2,4-triazole-3-thione derivatives

Levent Kandemir; Sevgi Karakuş; Suna Özbaş; Sevim Rollas; Julide Akbuğa

Synthesis, structure elucidation and cytotoxic activities of 2,5-disubstituted-1,3,4-thiadiazole and l,2,4-triazole-3-thione derivatives

Abstract

In this study, a series of 1,3,4-thiadiazole (1b-9b) and l,2,4-triazole-3-thione (1c-9c) derivatives were synthesized. The reaction proses was carried out with the cyclocondensation of suitable 1,4-disubstituted thiosemicarbazide derivatives (1a-9a). The structures of the synthesized compounds were confirmed by the data obtained from elemental analysis, HPLC, UV, IR, 1H-NMR and MS spectra. All of the compounds were tested for their cytotoxic activities against L929 fibroblast cells by MTT method. It was determined that the tested compounds 1a-9a, 1b-9b and 1c-9c were not cytotoxic at the studied concentrations (5.0 g/mL and 10.0 g/mL) in L929 cell lines. Compounds 1a-c, 2a-c, 3a-c, 4a-c, 5a-c and 8a-c showed increased growth inhibition whereas compounds 6a-c, 7a-c and 9a-c showed decreased growth inhibition on L929 cell lines

Keywords

References

[1] Othman A, Kihel M, Amara S. 1,3,4-Oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole derivatives as potential antibacterial agents. Arab J Chem. 2019; 12(7): 1660-1675. [CrossRef]
[2] Radwan A, Alanazi F, Al-Agamy M. 1,3,4-Thiadiazole and 1,2,4-triazole-3(4H)-thione bearing salicylate moiety: synthesis and evaluation as anti-Candida albicans. Braz J Pharm Sci. 2017; 53(1): 15239. [CrossRef]
[3] Cao X, Wang X, Wang S, Bao L. Asymmetric synthesis of novel triazole derivatives and their in vitro antiviral activity and mechanism of action. Eur J Med Chem. 2017; 139: 718-725. [CrossRef]
[4] Ayati A, Emami S, Foroumadi A. The importance of triazole scaffold in the development of anticonvulsant agents. Eur J Med Chem. 2016; 109: 380-392. [CrossRef]
[5] Vaishnav Y, Jha, K, Verma S, Kashyap P, and Kaur D. A Review on Antidiabetic Activity of Substituted 1,3,4-thiadiazole Derivatives. Res J Pharm Tech. 2017; 10 (2): 4467–4470. [CrossRef]
[6] Gökşen U, Kelekçi N, Göktaş Ö, Köysal Y, Kılıç E, Işık Ş, Aktay G, Özalp M. 1-Acylthiosemicarbazides, 1,2,4-triazole-5(4H)-thiones, 1,3,4-thiadiazoles and hydrazones containing 5-methyl-2-benzoxazolinones: Synthesis, analgesic-anti-inflammatory and antimicrobial activities. Bioorg Med Chem. 2007; 15(17): 5738-5751. [CrossRef]
[7] Palaska E, Şahin G, Kelicen P, Durlu N, Altinok G. Synthesis and anti-inflammatory activity of 1-acylthiosemicarbazides, 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazole-3-thiones. Farmaco. 2002; 57(2): 101-107. [CrossRef]
[8] Holla BS, Poorjary KN, Rao BS, Shivananda MK. New bis-aminomercaptotriazoles and bis-triazolothiadiazoles as possible anticancer agents. Eur J Med Chem. 2002; 37: 511–517. [CrossRef]

[9] Serban G, Stanasel O, Serban E, Bota S. 2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents. Drug Des Devel Ther. 2018; 12: 1545-1566. [CrossRef]
[10] Liu Y, Li J, Liu X, Li Z, Men Y, Sun Y, Chen B. Design, synthesis, and screening for the antiproliferative activity of new 1,3,4-thiadiazole scaffold linked to substituted phenacyl derivatives and disulfides. J Sulphur Chem. 2022; 43: 426-442. [CrossRef]
[11] Kharb R, Sharma PC, Yar MS. Pharmacological significance of triazole scaffold. J Enzyme Inhib Med Chem. 2009; 26(1): 1-21. [CrossRef]
[12] Zengin B, Tan OU, Arafa RK, Balkan A. Design and synthesis of new 2-oxoquinoxalinyl-1,2,4-triazoles as antitumor VEGFR-2 inhibitors. Bioorg Chem. 2022; 121: 105696. [CrossRef]
[13] Abdelli A, Azzouni S, Plais R, Gaucher A, Efrit ML, Prim D. Recent advances in the chemistry of 1,2,4-triazoles: Synthesis, reactivity and biological activities. Tetrahedron Lett. 2021; 86: 153518. [CrossRef]
[14] Aggarwal R, Sumran G. An insight on medicinal attributes of 1,2,4-triazoles. Eur J Med Chem. 2020; 205: 112652. [CrossRef]
[15] Tatar E, Küçükgüzel ŞG, Karakuş S, De Clercq E, Andrei G, Snoeck R, Pannecouque C, Öktem Okullu S, Ünübol N, Kocagöz T, Kalaycı S, Şahin F, Küçükgüzel İ. Synthesis and biological evaluation of some new 1,3,4-thiadiazole and 1,2,4-triazole derivatives from L-methionine as antituberculosis and antiviral agents. Marmara Pharm J. 2015; 19: 88-102. [CrossRef]
[16] Pitucha M, Janeczko M, Klimek K, Fornal E, Wos M, Pachuta-Stec A, Ginalska G, Kaczor AA. 1,2,4-Triazolin-5-thione derivatives with anticancer activity as CK1γ kinase inhibitors. Bioorg Chem. 2020; 99: 103806. [CrossRef]
[17] Zubets IV, Boikov YA, Viktorovskii IV, Vyunov KA. Synthesis and mass spectrophotometric study of 2-amino and 2-chloro-5aryl-1,3,4-thiadiazoles. Chem Hetero Comp. 1986; 22: 1148-1152. [CrossRef]
[18] Özger Y, Rollas S. Reductive cleavage of azo compounds with hydrazine and some 1,3,4-thiadiazole derivatives. J Pharm Univ Mar. 1988; 5: 133-141.
[19] Doğan HN, Rollas S, Erdeniz H. Synthesis, structure elucidation and antimicrobial activity of some 3-hydroxy-2-naphthoic acid hydrazide derivatives. Farmaco. 1998; 53: 462-467. [CrossRef]
[20] Willams DH. Mass Spectrometry Volume 2. 2005.
[21] Gülerman N, Rollas S, Kiraz M, Ekinci AC, Vidin A. Evaluation of antimycobacterial and anticonvulsant activities of new 1-(4-fluorobenzoyl)-4-substituted thiosemicarbazide and 5-(4-fluorophenyl)-4-substituted-2,4-dihydro-3H-1,2,4-triazole-3-thione derivatives. Farmaco. 1997; 52(11): 691-695. [CrossRef]
[22] Doğan HN, Duran A, Rollas S. Synthesis and preliminary anticancer activity of new 1H-4,5-dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-1,2,4-triazoline-5-thiones. Ind J Chem. 2005; 44(11): 2301-2307. [CrossRef]
[23] Küçükgüzel İ, Tatar E, Küçükgüzel G, Rollas S, De Clercq E. Synthesis of some novel thiourea derivatives obtained from 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones and evaluation as antiviral/anti HIV and anti-tuberculosis agents. Eur J Med Chem. 2008; 43: 381-392. [CrossRef]
[24] Karakuş S, Çoruh U, Barlas Durgun B, Vazquez Lopez E. M, Turan S, Akbuğa J, Rollas S. Synthesis and cytotoxic activity of some 1,2,4-triazoline-3-thione and 2,5-disubstituted-1,3,4-thiadiazole derivatives. Marmara Pharm J. 2010; 14: 84-90. [CrossRef]
[25] Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017; 7: 42717. [CrossRef]
[26] Kalyoncuoğlu N, Rollas S, Sür-Altıner D, Yeğenoğlu Y, Anğ Ö. 1-(p-Benzoylamino)benzoyl)-4-substituted thisemicarbazides: Synthesis and antibacterial and antifungal activities. Pharmazie. 1992; 47: 796-797. [CrossRef]
[27] Karakuş S, Rollas S. Synthesis and antituberculosis activity of new N-phenyl-N'-[4-5-alkyl/arylamino-1,3,4-thiadiazole-2-yl)phenyl]thioureas. Farmaco. 2002; 57(7): 577-581. [CrossRef]
[28] Rollas S, Kalyancıoğlu N, Sür-Altıner D, Yeğenoğlu Y. 5-(4-Aminophenyl)-4-substituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones: Synthesis and antibacterial and antifungal activities. Pharmazie. 1993; 48: 308-309. [CrossRef]

Details

Primary Language

English

Subjects

Pharmaceutical Biotechnology, Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Levent Kandemir This is me
Türkiye

Sevgi Karakuş ^*
0000-0002-7911-8372
Türkiye

Suna Özbaş
0000-0002-1721-7543
Türkiye

Sevim Rollas
0000-0002-4144-6952
Türkiye

Julide Akbuğa This is me
0000-0002-1693-9579
Türkiye

Publication Date

June 28, 2025

Submission Date

April 19, 2022

Acceptance Date

June 11, 2022

Published in Issue

Year 2022 Volume: 26 Number: 4

IZ

https://izlik.org/JA85BP68GM

Cite

RIS / Bibtex

APA

Kandemir, L., Karakuş, S., Özbaş, S., Rollas, S., & Akbuğa, J. (2025). Synthesis, structure elucidation and cytotoxic activities of 2,5-disubstituted-1,3,4-thiadiazole and l,2,4-triazole-3-thione derivatives. Journal of Research in Pharmacy, 26(4), 941-953. https://izlik.org/JA85BP68GM

AMA

1.Kandemir L, Karakuş S, Özbaş S, Rollas S, Akbuğa J. Synthesis, structure elucidation and cytotoxic activities of 2,5-disubstituted-1,3,4-thiadiazole and l,2,4-triazole-3-thione derivatives. J. Res. Pharm. 2025;26(4):941-953. https://izlik.org/JA85BP68GM

Chicago

Kandemir, Levent, Sevgi Karakuş, Suna Özbaş, Sevim Rollas, and Julide Akbuğa. 2025. “Synthesis, Structure Elucidation and Cytotoxic Activities of 2,5-Disubstituted-1,3,4-Thiadiazole and L,2,4-Triazole-3-Thione Derivatives”. Journal of Research in Pharmacy 26 (4): 941-53. https://izlik.org/JA85BP68GM.

EndNote

Kandemir L, Karakuş S, Özbaş S, Rollas S, Akbuğa J (June 1, 2025) Synthesis, structure elucidation and cytotoxic activities of 2,5-disubstituted-1,3,4-thiadiazole and l,2,4-triazole-3-thione derivatives. Journal of Research in Pharmacy 26 4 941–953.

IEEE

[1]L. Kandemir, S. Karakuş, S. Özbaş, S. Rollas, and J. Akbuğa, “Synthesis, structure elucidation and cytotoxic activities of 2,5-disubstituted-1,3,4-thiadiazole and l,2,4-triazole-3-thione derivatives”, J. Res. Pharm., vol. 26, no. 4, pp. 941–953, June 2025, [Online]. Available: https://izlik.org/JA85BP68GM

ISNAD

Kandemir, Levent - Karakuş, Sevgi - Özbaş, Suna - Rollas, Sevim - Akbuğa, Julide. “Synthesis, Structure Elucidation and Cytotoxic Activities of 2,5-Disubstituted-1,3,4-Thiadiazole and L,2,4-Triazole-3-Thione Derivatives”. Journal of Research in Pharmacy 26/4 (June 1, 2025): 941-953. https://izlik.org/JA85BP68GM.

JAMA

1.Kandemir L, Karakuş S, Özbaş S, Rollas S, Akbuğa J. Synthesis, structure elucidation and cytotoxic activities of 2,5-disubstituted-1,3,4-thiadiazole and l,2,4-triazole-3-thione derivatives. J. Res. Pharm. 2025;26:941–953.

MLA

Kandemir, Levent, et al. “Synthesis, Structure Elucidation and Cytotoxic Activities of 2,5-Disubstituted-1,3,4-Thiadiazole and L,2,4-Triazole-3-Thione Derivatives”. Journal of Research in Pharmacy, vol. 26, no. 4, June 2025, pp. 941-53, https://izlik.org/JA85BP68GM.

Vancouver

1.Levent Kandemir, Sevgi Karakuş, Suna Özbaş, Sevim Rollas, Julide Akbuğa. Synthesis, structure elucidation and cytotoxic activities of 2,5-disubstituted-1,3,4-thiadiazole and l,2,4-triazole-3-thione derivatives. J. Res. Pharm. [Internet]. 2025 Jun. 1;26(4):941-53. Available from: https://izlik.org/JA85BP68GM