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A New Series of Bis (Thiosemicarbazone) Derivatives: Synthesis, Spectroscopic Characterization, and Antioxidant Activities

Year 2025, Volume: 29 Issue: 5, 539 - 549, 27.10.2025
https://doi.org/10.16984/saufenbilder.1745320

Abstract

New bis (thiosemicarbazone) derivatives (1-5) were obtained from thiophene-2,5-dicarbaldehyde and numerous thiosemicarbazides. The thiosemicarbazides were prepared various isothiocyanates and hydrazine monohydrate. The structure elucidation of all obtained products were determined via routine spectroscopic techniques, including proton and carbon NMR (¹H, ¹³C), Fourier-transform infrared spectroscopy (FT-IR), and elemental composition analysis. In this research, the antioxidant activities of the newly synthesized compounds were assessed by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Based on the percentage of inhibition, the IC₅₀ values indicated the following order of activity: Trolox>1>3>4>2>5. Additionally, the reducing capabilities of the compounds were determined using the potassium ferricyanide reduction method. The absorbance values obtained from this assay for all the compounds were lower than that of Trolox, suggesting comparatively weaker reducing power. The study also explored how changes in molecular structure influence antioxidant activity, focusing especially on how various functional groups affect radical scavenging efficiency.

Thanks

We are also grateful to Assoc. Prof. Temel Kan Bakır at Kastamonu University for his contributions during antioxidant studies.

References

  • M. G. Gündüz, B. Kaya, C. Özkul, O. Şahin, E. M. Rekha, D. Sriram, B. Ülküseven, “S-alkylated thiosemicarbazone derivatives: Synthesis, crystal structure determination, antimicrobial activity evaluation and molecular docking studies,” Journal of Molecular Structure, vol. 1242, p. 130674, 2021.
  • H. Govender, C. Mocktar, H. M. Kumalo, N. A. Koorbanally, “Synthesis, antibacterial activity and docking studies of substituted quinolone thiosemicarbazones,” Phosphorus, Sulfur, and Silicon and the Related Elements, vol. 194, no. 11, pp. 1074-1081, 2019.
  • W. Hernández, F. Carrasco, A. Vaisberg, E. Spodine, M. Icker, H. Krautscheid, L. Beyer, C. Tamariz-Angeles, P. Olivera-Gonzales, “Novel thiosemicarbazone derivatives from furan-2-carbaldehyde: synthesis, characterization, crystal structures, and antibacterial, antifungal, antioxidant, and antitumor activities,” Journal of Chemistry, vol. 2023, pp. 1-20, 2023.
  • M. S. Çavuş, “Synthesis of new 5-iodoisatin derivatives: Predicting antioxidant inhibition activity with DFT studies,” Journal of Molecular Structure, vol. 1323, p. 140826, 2025.
  • P. P. Netalkar, S. P. Netalkar, V. K. Revankar, “Nickel (II) complexes of thiosemicarbazones: Synthesis, characterization, X-ray crystallographic studies and in vitro antitubercular and antimicrobial studies,” Transition Metal Chemistry, vol. 39, pp. 519-526, 2014.
  • B. Shakya, P. N. Yadav, “Thiosemicarbazones as potent anticancer agents and their modes of action,” Mini Reviews in Medicinal Chemistry, vol. 20, no. 8, pp. 638-661, 2020.
  • Z. Ş. Sevinçli, G. N. Duran, M. Özbil, N. Karalı, “Synthesis, molecular modeling and antiviral activity of novel 5-fluoro-1H-indole-2, 3-dione 3-thiosemicarbazones,” Bioorganic Chemistry, vol. 104, p. 104202, 2020.
  • H. Pervez, N. Manzoor, M. Yaqub, A. Khan, K. M. Khan, F.-u.-H. Nasim, M. I. Choudhary, “Synthesis and urease inhibitory properties of some new N4-substituted 5-nitroisatin-3-thiosemicarbazones,” Letters in Drug Design & Discovery, vol. 7, no. 2, pp. 102-108, 2010.
  • A. Kshirsagar, M. P. Toraskar, V. M. Kulkarni, S. Dhanashire, V. Kadam, “Microwave assisted synthesis of potential anti infective and anticonvulsant thiosemicarbazones,” International Journal of ChemTech Research, vol. 1, no. 3, pp. 696-701, 2009.
  • A. A. Al-Amiery, Y. K. Al-Majedy, H. H. Ibrahim, A. A. Al-Tamimi, “Antioxidant, antimicrobial, and theoretical studies of the thiosemicarbazone derivative Schiff base 2-(2-imino-1-methylimidazolidin-4-ylidene) hydrazinecarbothioamide (IMHC),” Organic and Medicinal Chemistry Letters, vol. 2, no. 1, p. 4, 2012.
  • H. Pervez, M. S. Iqbal, M. Y. Tahir, F. H. Nasim, M. I. Choudhary, K. M. Khan, “In vitro cytotoxic, antibacterial, antifungal and urease inhibitory activities of some N4-substituted isatin-3-thiosemicarbazones,” Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 23, no. 6, pp. 848-854, 2008.
  • H. Muğlu, “Synthesis, characterization, and antioxidant activity of some new N4-arylsubstituted-5-methoxyisatin-β-thiosemicarbazone derivatives,” Research on Chemical Intermediates, pp. 1-16, 2020.
  • F. S. Tokalı, P. Taslimi, H. Usanmaz, M. Karaman, K. Şendil, “Synthesis, characterization, biological activity and molecular docking studies of novel schiff bases derived from thiosemicarbazide: Biochemical and computational approach,” Journal of Molecular Structure, vol. 1231, p. 129666, 2021.
  • T. R. Bal, B. Anand, P. Yogeeswari, D. Sriram, “Synthesis and evaluation of anti-HIV activity of isatin β-thiosemicarbazone derivatives,” Bioorganic & Medicinal Chemistry Letters, vol. 15, no. 20, pp. 4451-4455, 2005.
  • M. A. Arafath, “Thiosemicarbazone Schiff base ligands and their complexes with nickel, palladium and platinum show anticancer and antibacterial activities,” Journal of Sulfur Chemistry, vol. 45, no. 1, pp. 138-171, 2024.
  • F. G. Karakuş, S. Tunalı, T. Bal-Demirci, B. Ülküseven, R. Yanardağ, “Ameliorative effect of a vanadium-thiosemicarbazone complex on oxidative stress in stomach tissue of experimental diabetic rats,” Sakarya University Journal of Science, vol. 28, no. 1, pp. 133-144, 2024.
  • G. Subhashree, J. Haribabu, S. Saranya, P. Yuvaraj, D. A. Krishnan, R. Karvembu, D. Gayathri, “In vitro antioxidant, antiinflammatory and in silico molecular docking studies of thiosemicarbazones,” Journal of Molecular Structure, vol. 1145, pp. 160-169, 2017.
  • J. Robak, E. Marcinkiewicz, “Scavenging of reactive oxygen species as the mechanism of drug action,” Polish Journal of Pharmacology, vol. 47, no. 2, pp. 89-98, 1995.
  • K. Krumova, G. Cosa, “Overview of reactive oxygen species,” Singlet Oxygen: Applications in Biosciences and Nanosciences, vol. 1, pp. 1-21, 2016.
  • L. Wang, Z. Kuang, D. Zhang, Y. Gao, M. Ying, T. Wang, “Reactive oxygen species in immune cells: A new antitumor target,” Biomedicine and Pharmacotherapy, vol. 133, p. 110978, 2021.
  • Y. Ünver, K. Sancak, F. Çelik, E. Birinci, M. Küçük, S. Soylu, N. A. Burnaz, “New thiophene-1, 2, 4-triazole-5 (3)-ones: Highly bioactive thiosemicarbazides, structures of Schiff bases and triazole–thiols,” European Journal of Medicinal Chemistry, vol. 84, pp. 639-650, 2014.
  • A. Bhardwaj, A. Dubey, A. Tufail, N. Tufail, M. Kumar, S. Garg, “Unveiling the biomedical potential of thiophene‐derived Schiff base complexes: A comprehensive study of synthesis, spectral characterization, antimicrobial efficacy, antioxidant activity, and computational insights,” Applied Organometallic Chemistry, vol. 38, no. 5, p. e7398, 2024.
  • K. Ozturk, M. S. Tanyildizi, H. Ciftci, O. G. Aytac, “Synthesis of thiophene-based imine and phosphoazometine compounds: in vitro antiproliferative, antimicrobial, antioxidant, carbonic anhydrase I and II enzyme inhibition evaluations and molecular docking study,” Chemical Papers, pp. 1-17, 2025.
  • R. Apak, K. Güçlü, B. Demirata, M. Özyürek, S. E. Çelik, B. Bektaşoğlu, K. I. Berker, D. Özyurt, “Comparative evaluation of various total antioxidant capacity assays applied to phenolic compounds with the CUPRAC assay,” Molecules, vol. 12, no. 7, pp. 1496-1547, 2007.
  • İ. Gülçin, “Fe3+ – Fe2+ transformation method: An important antioxidant assay,” in Advanced Protocols in Oxidative Stress III: Springer, pp. 233-246, 2014.
  • A. Mermer, S. Alyar, “Synthesis, characterization, DFT calculation, antioxidant activity, ADMET and molecular docking of thiosemicarbazide derivatives and their Cu (II) complexes,” Chemico-Biological Interactions, vol. 351, p. 109742, 2022.
  • M. M. F. Leal, M. F. D. Silva, D. S. C. Marques, R. F. V. Mendes, R. M. Ximenes, D. C. Machado, J. J. D. Silva, C. G. Rodrigues, I. J. D. C. Filho, M. D. C. A. D. Lima, “Preliminary evaluation of the toxicological, antioxidant and antitumor activities promoted by the compounds 2, 4-dihydroxy-benzylidene-thiosemicarbazones an in silico, in vitro and in vivo study,” Anais da Academia Brasileira de Ciências, vol. 96, no. 2, p. e20231247, 2024.
  • Y. M. Zhang, D. D. Wang, Q. Lin, T. B. Wei, “Synthesis and anion recognition properties of thiosemicarbazone based molecular tweezers,” Phosphorus, Sulfur, and Silicon and the Related Elements, vol. 183, no. 1, pp. 44-55, 2007.
  • H. Yakan, “Preparation, structure elucidation, and antioxidant activity of new bis (thiosemicarbazone) derivatives,” Turkish Journal of Chemistry, vol. 44, no. 4, p. 1085, 2020.
  • W. Brand-Williams, M. E. Cuvelier, C. Berset, “Use of a free radical method to evaluate antioxidant activity,” LWT-Food Science and Technology, vol. 28, no. 1, pp. 25-30, 1995.
  • F. Sönmez, E. Akgün, Z. Şahin, “Synthesis, DPPH and ABTS activity of novel furfuryl-chalcone derivatives,” Sakarya University Journal of Science, vol. 26, no. 6, pp. 1224-1232, 2022.
  • N. T. Karakullukçu, “The Impact of Hypericum perforatum L. as an Organic Free-Radical Scavenger in Biodiesel-Diesel Blends,” Sakarya University Journal of Science, vol. 29, no. 1, pp. 100-112, 2025.
  • V. Bondet, W. Brand-Williams, C. Berset, “Kinetics and mechanisms of antioxidant activity using the DPPH. free radical method,” LWT-Food Science and Technology, vol. 30, no. 6, pp. 609-615, 1997.
  • N. Naik, H. Vijay Kumar, P. B. Vidyashree, “Synthesis and evaluation of antioxidant potential of novel isatin analogues,” Journal of Pharmacy Research, vol. 4, no. 8, pp. 2686-2689, 2011.
  • E. N. Frankel, A. S. Meyer, “The problems of using one‐dimensional methods to evaluate multifunctional food and biological antioxidants,” Journal of the Science of Food and Agriculture, vol. 80, no. 13, pp. 1925-1941, 2000.
  • F. Afroze, M. T. Hossain, “Proximate analysis, phytochemical screening and antioxidant activity of Psidium guajava leaves growing in coastal area of Bangladesh,” World Journal of Pharmacy and Pharmaceutical Sciences, vol. 4, no. 5, pp. 140-51, 2015.
  • M. Oyaizu, “Studies on products of browning reaction antioxidative activities of products of browning reaction prepared from glucosamine,” The Japanese Journal of Nutrition and Dietetics, vol. 44, no. 6, pp. 307-315, 1986.
  • T. K. Bakır, “New 5-methylisatin-thiosemicarbazones: preparation, spectroscopic study and antioxidant properties,” Research on Chemical Intermediates, vol. 50, no. 11, pp. 5593-5615, 2024.
  • A. A. Al-Amiery, Y. K. Al-Majedy, H. H. Ibrahim, A. A. Al-Tamimi, “Antioxidant, antimicrobial, and theoretical studies of the thiosemicarbazone derivative Schiff base 2-(2-imino-1-methylimidazolidin-4-ylidene) hydrazinecarbothioamide (IMHC),” Organic and Medicinal Chemistry Letters, vol. 2, no. 4, pp. 1-7, 2012.
  • H. Yakan, M. Azam, S. Kansız, H. Muğlu, M. Ergül, P. Taslimi, Ü. M. Koçyiğit, M. Karaman, S. I. Al-Resayes, K. Min, “Isatin/thiosemicarbohydrazone hybrids: Facile synthesis, and their evaluation as anti-proliferatıve agents and metabolıc enzyme inhibitors,” Bulletin of the Chemical Society of Ethiopia, vol. 37, no. 5, pp. 1221-1236, 2023.
  • H. Yakan, H. Muğlu, C. Türkeş, Y. Demir, M. Erdoğan, M. S. Çavuş, Ş. Beydemir, “A novel series of thiosemicarbazone hybrid scaffolds: Design, synthesis, DFT studies, metabolic enzyme inhibition properties, and molecular docking calculations,” Journal of Molecular Structure, vol. 1280, p. 135077, 2023.
  • I. Fleming, D. Williams, Spectroscopic methods in organic chemistry, Seventh Edition ed. Switzerland: Springer Nature, 2020.
  • S. F. Barbuceanu, D. C. Ilies, G. Saramet, V. Uivarosi, C. Draghici, V. Radulescu, “Synthesis and antioxidant activity evaluation of new compounds from hydrazinecarbothioamide and 1, 2, 4-triazole class containing diarylsulfone and 2, 4-difluorophenyl moieties,” International Journal of Molecular Sciences, vol. 15, no. 6, pp. 10908-10925, 2014.
  • S. Eğlence-Bakır, “Synthesis and antioxidant activities of new nickel (II) complexes derived from 4-benzyloxysalicylidene-S-methyl/propyl thiosemicarbazones,” Turkish Journal of Chemistry, vol. 45, no. 3, pp. 835-844, 2021.
  • F. Qi, Q. Qi, J. Song, J. Huang, “Synthesis, Crystal Structure, Biological Evaluation and in Silico Studies on Novel (E)‐1‐(Substituted Benzylidene)‐4‐(3‐isopropylphenyl) thiosemicarbazone Derivatives,” Chemistry & Biodiversity, vol. 18, no. 2, p. e2000804, 2021.
There are 45 citations in total.

Details

Primary Language English
Subjects Organic Chemistry (Other)
Journal Section Research Article
Authors

Hasan Yakan 0000-0002-4428-4696

Halit Muğlu 0000-0001-8306-2378

Submission Date July 18, 2025
Acceptance Date September 3, 2025
Early Pub Date October 21, 2025
Publication Date October 27, 2025
Published in Issue Year 2025 Volume: 29 Issue: 5

Cite

APA Yakan, H., & Muğlu, H. (2025). A New Series of Bis (Thiosemicarbazone) Derivatives: Synthesis, Spectroscopic Characterization, and Antioxidant Activities. Sakarya University Journal of Science, 29(5), 539-549. https://doi.org/10.16984/saufenbilder.1745320
AMA Yakan H, Muğlu H. A New Series of Bis (Thiosemicarbazone) Derivatives: Synthesis, Spectroscopic Characterization, and Antioxidant Activities. SAUJS. October 2025;29(5):539-549. doi:10.16984/saufenbilder.1745320
Chicago Yakan, Hasan, and Halit Muğlu. “A New Series of Bis (Thiosemicarbazone) Derivatives: Synthesis, Spectroscopic Characterization, and Antioxidant Activities”. Sakarya University Journal of Science 29, no. 5 (October 2025): 539-49. https://doi.org/10.16984/saufenbilder.1745320.
EndNote Yakan H, Muğlu H (October 1, 2025) A New Series of Bis (Thiosemicarbazone) Derivatives: Synthesis, Spectroscopic Characterization, and Antioxidant Activities. Sakarya University Journal of Science 29 5 539–549.
IEEE H. Yakan and H. Muğlu, “A New Series of Bis (Thiosemicarbazone) Derivatives: Synthesis, Spectroscopic Characterization, and Antioxidant Activities”, SAUJS, vol. 29, no. 5, pp. 539–549, 2025, doi: 10.16984/saufenbilder.1745320.
ISNAD Yakan, Hasan - Muğlu, Halit. “A New Series of Bis (Thiosemicarbazone) Derivatives: Synthesis, Spectroscopic Characterization, and Antioxidant Activities”. Sakarya University Journal of Science 29/5 (October2025), 539-549. https://doi.org/10.16984/saufenbilder.1745320.
JAMA Yakan H, Muğlu H. A New Series of Bis (Thiosemicarbazone) Derivatives: Synthesis, Spectroscopic Characterization, and Antioxidant Activities. SAUJS. 2025;29:539–549.
MLA Yakan, Hasan and Halit Muğlu. “A New Series of Bis (Thiosemicarbazone) Derivatives: Synthesis, Spectroscopic Characterization, and Antioxidant Activities”. Sakarya University Journal of Science, vol. 29, no. 5, 2025, pp. 539-4, doi:10.16984/saufenbilder.1745320.
Vancouver Yakan H, Muğlu H. A New Series of Bis (Thiosemicarbazone) Derivatives: Synthesis, Spectroscopic Characterization, and Antioxidant Activities. SAUJS. 2025;29(5):539-4.


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