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

Yıl 2022, Cilt: 26 Sayı: 4, 941 - 953, 28.06.2025

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

Öz

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

Anahtar Kelimeler

Acid hydrazide cytotoxicity 1-3-4thiadiazole 1-4disubstituted thiosemicarbazide 1-2-4triazole-3-thione.

Kaynakça

  • [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]

Yıl 2022, Cilt: 26 Sayı: 4, 941 - 953, 28.06.2025

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

Öz

Kaynakça

  • [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]
Toplam 28 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmasotik Biyoteknoloji, Farmasotik Kimya
Bölüm Articles
Yazarlar

Levent Kandemir

Sevgi Karakuş 0000-0002-7911-8372

Suna Özbaş 0000-0002-1721-7543

Sevim Rollas 0000-0002-4144-6952

Julide Akbuğa 0000-0002-1693-9579

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2022 Cilt: 26 Sayı: 4

Kaynak Göster

APA Kandemir, L., Karakuş, S., Özbaş, S., Rollas, S., vd. (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.
AMA 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. Haziran 2025;26(4):941-953.
Chicago Kandemir, Levent, Sevgi Karakuş, Suna Özbaş, Sevim Rollas, ve Julide Akbuğa. “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, sy. 4 (Haziran 2025): 941-53.
EndNote Kandemir L, Karakuş S, Özbaş S, Rollas S, Akbuğa J (01 Haziran 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 L. Kandemir, S. Karakuş, S. Özbaş, S. Rollas, ve 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., c. 26, sy. 4, ss. 941–953, 2025.
ISNAD Kandemir, Levent vd. “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 (Haziran 2025), 941-953.
JAMA 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 vd. “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, c. 26, sy. 4, 2025, ss. 941-53.
Vancouver 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):941-53.