Journals / Sakarya University Journal of Science / 2026 / Volume: 30 Issue: 1

Novel Isatin-Derived Thiosemicarbazones: Synthesis, Characterization, and Assessment of Antioxidant Activity

Hasan Yakan(ONDOKUZ MAYIS ÜNİVERSİTESİ)0000-0002-4428-4696
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Publication Date
2026-02-04
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AI Summary & Key Takeaways

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⚡ TL;DR(Too Long; Didn't Read)

Particular attention was given to the relationship between structural modifications and antioxidant activity, with a focus on how different functional groups influence the compounds' ability to neutralize free radicals.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:A series of new of isatin-derived thiosemicarbazones (1–8) were synthesized using different isatin derivatives and N-(4-ethylphenyl)hydrazinecarbothioamide.
📊
Key Findings & Data:The intermediated thiosemicarbazide was obtained by the reaction of 1-ethyl-4-isothiocyanatobenzene with hydrazine monohydrate.
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Conclusion & Impact:Particular attention was given to the relationship between structural modifications and antioxidant activity, with a focus on how different functional groups influence the compounds' ability to neutralize free radicals.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Isatin · Thiosemicarbazone · Spectroscopic methods

Abstract

A series of new of isatin-derived thiosemicarbazones (1–8) were synthesized using different isatin derivatives and N-(4-ethylphenyl)hydrazinecarbothioamide. The intermediated thiosemicarbazide was obtained by the reaction of 1-ethyl-4-isothiocyanatobenzene with hydrazine monohydrate. The identities and purities of all newly compounds were confirmed through standard spectroscopic techniques, including proton and carbon nuclear magnetic resonance (¹H and ¹³C NMR), Fourier-transform infrared (FT-IR) spectroscopy, and elemental analysis. In this study, the antioxidant potential of the newly synthesized compounds was evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH•) free radical scavenging assay. Compound 7 showed higher activity than the standard Trolox and the other compounds. The remaining compounds exhibited lower activity than the standard. The IC50 values of the compounds were determined to range from 15.88 ± 1.21 to 145.34 ± 2.68 μM. The antioxidant activity of the compounds decreased in the following order: 7 > 2 > 3 > 8 > 6 > 5 > 4 > 1. Particular attention was given to the relationship between structural modifications and antioxidant activity, with a focus on how different functional groups influence the compounds' ability to neutralize free radicals.

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Cite This Article

Yakan, H. (2026). Novel Isatin-Derived Thiosemicarbazones: Synthesis, Characterization, and Assessment of Antioxidant Activity. Sakarya University Journal of Science, Volume: 30 Issue: 1. https://doi.org/10.16984/saufenbilder.1777659

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References (51)

  1. H. Pervez, et al., "Synthesis and urease inhibitory properties of some new N4-substituted 5-nitroisatin-3-thiosemicarbazones", Lett. Drug Des. Discov., vol. 7, no. 2, pp. 102–108, Feb 2010. doi: 10.2174/157018010790225840. [Online]. Available: https://doi.org/10.2174/157018010790225840
  2. M. Islam, et al., "Synthesis and characterization of new thiosemicarbazones, as potent urease inhibitors: In vitro and in silico studies," Bioorg. Chem., vol. 87, pp. 155–162, June 2019. doi: 10.1016/j.bioorg.2019.03.008. [Online]. Available: https://doi.org/10.1016/j.bioorg.2019.03.008
  3. F. Rizvi, M. Khan, S. Z. A. M. Shah, M. Ali, and H. Siddiqui, "New thiosemicarbazone analogues: synthesis, urease inhibition, kinetics and molecular docking studies," Phosphorus Sulfur Silicon Relat. Elem., vol. 199, no. 5, pp. 394–405, May 2024. doi: 10.1080/10426507.2024.2354727. [Online]. Available: https://doi.org/10.1080/10426507.2024.2354727
  4. M. M. Aly, Y. A. Mohamed, K. A. El-Bayouki, W. M. Basyouni, and S. Y. Abbas, "Synthesis of some new 4 (3H)-quinazolinone-2-carboxaldehyde thiosemicarbazones and their metal complexes and a study on their anticonvulsant, analgesic, cytotoxic and antimicrobial activities–Part-1," Eur. J. Med. Chem., vol. 45, no. 8, pp. 3365–3373, Aug 2010. doi: 10.1016/j.ejmech.2010.04.020. [Online]. Available: https://doi.org/10.1016/j.ejmech.2010.04.020
  5. A. Q. Ali, et al., "Synthesis, structure and in vitro anticancer, DNA binding and cleavage activity of palladium (II) complexes based on isatin thiosemicarbazone derivatives," Appl. Organomet. Chem., vol. 31, no. 12, p. e3813, Dec 2017. doi: /10.1002/aoc.3813. [Online]. Available: https://doi.org/10.1002/aoc.3813
  6. A. Czylkowska, et al., "Thiosemicarbazone-based compounds: a promising scaffold for developing antibacterial, antioxidant, and anticancer therapeutics," Molecules, vol. 30, no. 1, p. 129, Jan 2024. doi: 10.3390/molecules30010129. [Online]. Available: https://doi.org/10.3390/molecules30010129
  7. P. P. Netalkar, S. P. Netalkar, and V. K. Revankar, "Nickel (II) complexes of thiosemicarbazones: synthesis, characterization, X-ray crystallographic studies and in vitro antitubercular and antimicrobial studies," Transition Met. Chem., vol. 39, pp. 519–526, June 2014. doi: 10.1007/s11243-014-9827-8. [Online]. Available: https://doi.org/10.1007/s11243-014-9827-8
  8. M. Süleymanoğlu, et al., "Synthesis, structural, cytotoxic and pharmacokinetic evaluation of some thiosemicarbazone derivatives," J. Biochem. Mol. Toxicol., vol. 34, no. 8, p. e22512, Aug 2020. doi: 10.1002/jbt.22512. [Online]. Available: https://doi.org/10.1002/jbt.22512
  9. W. M. Basyouni, S. Y. Abbas, K. A. El-Bayouki, R. M. Daawod, and M. K. Elawady, "Synthesis and antiviral evaluation of 5-(arylazo) salicylaldehyde thiosemicarbazone derivatives as potent anti-bovine viral diarrhea virus agents," Synth. Commun., vol. 51, no. 14, pp. 2168–2174, July 2021. doi: 10.1080/00397911.2021.1925298. [Online]. Available: https://doi.org/10.1080/00397911.2021.1925298
  10. W. Hernández, et al., "Novel thiosemicarbazone derivatives from furan-2-carbaldehyde: synthesis, characterization, crystal structures, and antibacterial, antifungal, antioxidant, and antitumor activities," J. Chem., vol. 2023, pp. 1–20, Oct 2023. doi: 10.1155/2023/5413236. [Online]. Available: https://doi.org/10.1155/2023/5413236
  11. M. S. Çavuş, "Synthesis of new 5-iodoisatin derivatives: Predicting antioxidant inhibition activity with DFT studies," J. Mol. Struct., vol. 1323, p. 140826, Mar 2025. doi: 10.1016/j.molstruc.2024.140826. [Online]. Available: https://doi.org/10.1016/j.molstruc.2024.140826
  12. H. Govender, C. Mocktar, H. M. Kumalo, and N. A. Koorbanally, "Synthesis, antibacterial activity and docking studies of substituted quinolone thiosemicarbazones," Phosphorus Sulfur Silicon Relat. Elem., vol. 194, no. 11, pp. 1074–1081, Nov 2019. doi: 10.1080/10426507.2019.1618298. [Online]. Available: https://doi.org/10.1080/10426507.2019.1618298
  13. M. G. Gündüz, et al., "S-alkylated thiosemicarbazone derivatives: Synthesis, crystal structure determination, antimicrobial activity evaluation and molecular docking studies," J. Mol. Struct., vol. 1242, p. 130674, Oct 2021. doi: 10.1016/j.molstruc.2021.130674. [Online]. Available: https://doi.org/10.1016/j.molstruc.2021.130674
  14. S. Pandeya, D. Sriram, G. Nath, and E. DeClercq, "Synthesis, antibacterial, antifungal and anti-HIV activities of Schiff and Mannich bases derived from isatin derivatives and N-[4-(4′-chlorophenyl) thiazol-2-yl] thiosemicarbazide," Eur. J. Pharm. Sci., vol. 9, no. 1, pp. 25–31, Oct 1999. doi: 10.1016/S0928-0987(99)00038-X. [Online]. Available: https://doi.org/10.1016/S0928-0987(99)00038-X
  15. G. Singh, et al., "Molecular design, synthesis, computational screening, antimicrobial evaluation and molecular docking study of acetylinic isatin hybrids," ChemistrySelect, vol. 3, no. 6, pp. 1942–1952, Feb 2018. doi: 10.1002/slct.201703051. [Online]. Available: https://doi.org/10.1002/slct.201703051
  16. A. Y. Alzahrani, Y. A. Ammar, M. A. Salem, M. Abu‐Elghait, and A. Ragab, "Design, synthesis, molecular modeling, and antimicrobial potential of novel 3‐[(1H‐pyrazol‐3‐yl) imino] indolin‐2‐one derivatives as DNA gyrase inhibitors," Arch. Pharm., vol. 355, no. 1, p. 2100266, Jan 2022. doi: 10.1002/ardp.202100266. [Online]. Available: https://doi.org/10.1002/ardp.202100266
  17. H. Yakan, T. K. Bakır, M. S. Çavuş and H. Muğlu, "New β-isatin aldehyde-N, N′-thiocarbohydrazones: preparation, spectroscopic studies and DFT approach to antioxidant characteristics", Res. Chem. Intermed., vol. 46, no. 12, pp. 5417–5440, Dec 2020. doi: 10.1007/s11164-020-04270-0. [Online]. Available: https://doi.org/10.1007/s11164-020-04270-0
  18. H. Yakan, et al., "A new series of asymmetric bis-isatin derivatives containing urea/thiourea moiety: Preparation, spectroscopic elucidation, antioxidant properties and theoretical calculations," J. Mol. Struct., vol. 1239, p. 130495, Oct 2021. doi: 10.1016/j.molstruc.2021.130495. [Online]. Available: https://doi.org/10.1016/j.molstruc.2021.130495
  19. S. H. Sumrra, et al., "Coordination behavior, structural, statistical and theoretical investigation of biologically active metal-based isatin compounds," Chem. Pap., vol. 76, no. 6, pp. 3705–3727, June 2022. doi: 10.1007/s11696-022-02123-1. [Online]. Available: https://doi.org/10.1007/s11696-022-02123-1
  20. H. Guo, "Isatin derivatives and their anti-bacterial activities," Eur. J. Med. Chem., vol. 164, pp. 678–688, Feb 2019. doi: 10.1016/j.ejmech.2018.12.017. [Online]. Available: https://doi.org/10.1016/j.ejmech.2018.12.017
  21. A. Y. Alzahrani, et al., "Development of novel indolin-2-one derivative incorporating thiazole moiety as DHFR and quorum sensing inhibitors: Synthesis, antimicrobial, and antibiofilm activities with molecular modelling study," Bioorg. Chem., vol. 119, p. 105571, Feb 2022. doi: 10.1016/j.bioorg.2021.105571. [Online]. Available: https://doi.org/10.1016/j.bioorg.2021.105571
  22. A. Jarrahpour et., "Synthesis, in-vitro biological evaluation, and molecular docking study of novel spiro-β-lactam-isatin hybrids", Med. Chem. Res., vol. 31, no. 6, pp. 1026–1034, June 2022. doi: 10.1007/s00044-022-02898-8. [Online]. Available: https://doi.org/10.1007/s00044-022-02898-8
  23. V. S. Pawar, et al., "Design, docking study and ADME prediction of Isatin derivatives as anti-HIV agents," Med. Chem. Res., vol. 20, no. 3, pp. 370–380, Apr 2011. doi: 10.1007/s00044-010-9329-y [Online]. Available: https://doi.org/10.1007/s00044-010-9329-y
  24. Ö. Güzel-Akdemir, A. Akdemir, N. Karalı, and C. T. Supuran, "Discovery of novel isatin-based sulfonamides with potent and selective inhibition of the tumor-associated carbonic anhydrase isoforms IX and XII," Org. Biomol. Chem., vol. 13, no. 23, pp. 6493–6499, June 2015. doi: 10.1039/C5OB00688K. [Online]. Available: https://doi.org/10.1039/C5OB00688K
  25. Y. Kaya, A. Erçağ, Y. Zorlu, Y. Demir, and İ. Gülçin, "New Pd (II) complexes of the bisthiocarbohydrazones derived from isatin and disubstituted salicylaldehydes: Synthesis, characterization, crystal structures and inhibitory properties against some metabolic enzymes," JBIC J. Biol. Inorg. Chem., vol. 27, no. 2, pp. 271–281, Mar 2022. doi: 10.1007/s00775-022-01932-9. [Online]. Available: https://doi.org/10.1007/s00775-022-01932-9
  26. Y. A. Ammar, et al., "Design, synthesis, antiproliferative activity, molecular docking and cell cycle analysis of some novel (morpholinosulfonyl) isatins with potential EGFR inhibitory activity," Eur. J. Med. Chem., vol. 156, pp. 918–932, Aug 2018. doi: 10.1016/j.ejmech.2018.06.061. [Online]. Available: https://doi.org/10.1016/j.ejmech.2018.06.061
  27. R. Meleddu, et al., "Investigating the anticancer activity of isatin/dihydropyrazole hybrids," ACS Med. Chem. Lett., vol. 10, no. 4, pp. 571–576, Apr 2018. doi: 10.1021/acsmedchemlett.8b00596. [Online]. Available: https://doi.org/10.1021/acsmedchemlett.8b00596
  28. S. Y. Abbas, et al., "Synthesis, characterization, and antiviral activity of novel fluorinated isatin derivatives," Monatsh. Chem., vol. 144, no. 11, pp. 1725–1733, Nov 2013. doi: 10.1007/s00706-013-1034-3. [Online]. Available: https://doi.org/10.1007/s00706-013-1034-3
  29. A. Jarrahpour, J. Sheikh, I. El Mounsi, H. Juneja, and T. B. Hadda, "Computational evaluation and experimental in vitro antibacterial, antifungal and antiviral activity of bis-Schiff bases of isatin and its derivatives," Med. Chem. Res., vol. 22, no. 3, pp. 1203–1211, Mar 2013. doi: 10.1007/s00044-012-0127-6. [Online]. Available: https://doi.org/10.1007/s00044-012-0127-6
  30. E. A. Fayed, A. Ragab, R. R. E. Eldin, A. H. Bayoumi, and Y. A. Ammar, "In vivo screening and toxicity studies of indolinone incorporated thiosemicarbazone, thiazole and piperidinosulfonyl moieties as anticonvulsant agents," Bioorg. Chem., vol. 116, p. 105300, Nov 2021. doi: 10.1016/j.bioorg.2021.105300. [Online]. Available: https://doi.org/10.1016/j.bioorg.2021.105300
  31. T. Aboul-Fadl, F. A. Bin-Jubair, and O. Aboul-Wafa, "Schiff bases of indoline-2, 3-dione (isatin) derivatives and nalidixic acid carbohydrazide, synthesis, antitubercular activity and pharmacophoric model building," Eur. J. Med. Chem., vol. 45, no. 10, pp. 4578–4586, Oct 2010. doi: 10.1016/j.ejmech.2010.07.020. [Online]. Available: https://doi.org/10.1016/j.ejmech.2010.07.020
  32. R. P. Chinnasamy, R. Sundararajan, and S. Govindaraj, "Synthesis, characterization, and analgesic activity of novel schiff base of isatin derivatives," J. Adv. Pharm. Technol. Res., vol. 1, no. 3, pp. 342-347, July 2010. doi: 10.4103/0110-5558.72428. [Online]. Available: https://doi.org/10.4103/0110-5558.72428
  33. J. Robak and E. Marcinkiewicz, "Scavenging of reactive oxygen species as the mechanism of drug action," Pol. J. Pharmacol., vol. 47, no. 2, pp. 89–98, Mar 1995. [Online]. Available: https://europepmc.org/article/med/8688896
  34. K. Krumova and G. Cosa, "Overview of reactive oxygen species," in Singlet Oxygen: Applications in Biosciences and Nanosciences, vol. 1, pp. 1–21, 2016. doi: 10.1039/9781782622208-00001. [Online]. Available: https://doi.org/10.1039/9781782622208-00001
  35. L. Wang, et al., "Reactive oxygen species in immune cells: A new antitumor target," Biomed. Pharmacother., vol. 133, p. 110978, Jan 2021. doi: 10.1016/j.biopha.2020.110978. [Online]. Available: https://doi.org/10.1016/j.biopha.2020.110978
  36. B. Z. Kurt, I. Gazioglu, F. Sonmez, and M. Kucukislamoglu, "Synthesis, antioxidant and anticholinesterase activities of novel coumarylthiazole derivatives," Bioorg. Chem., vol. 59, pp. 80–90, Apr 2015. doi: 10.1016/j.bioorg.2015.02.002. [Online]. Available: https://doi.org/10.1016/j.bioorg.2015.02.002
  37. B. Z. Kurt, I. Gazioglu, N. O. Kandas, and F. Sonmez, "Synthesis, anticholinesterase, antioxidant, and anti‐aflatoxigenic activity of novel coumarin carbamate derivatives," ChemistrySelect, vol. 3, no. 14, pp. 3978–3983, Apr 2018. doi: 10.1002/slct.201800142. [Online]. Available: https://doi.org/10.1002/slct.201800142
  38. I. J. Kang et al., "Isatin-β-thiosemicarbazones as potent herpes simplex virus inhibitors", Bioorg. Med. Chem. Lett., vol. 21, no. 7, pp. 1948–1952, Apr 2011. doi: 10.1016/j.bmcl.2011.02.037. [Online]. Available: https://doi.org/10.1016/j.bmcl.2011.02.037
  39. M. S. Blois, "Antioxidant determinations by the use of a stable free radical," Nature, vol. 181, no. 4617, pp. 1199–1200, Apr 1958. doi: 10.1038/1811199a0. [Online]. Available: https://doi.org/10.1038/1811199a0
  40. S. Yenigun, et al., "DNA protection, molecular docking, molecular dynamic, enzyme inhibition, and kinetics studies of apigenin isolated from Nepeta baytopii Hedge & Lamond by bioactivity-guided fractionation," J. Biomol. Struct. Dyn., vol. 43, no. 16, pp. 9404–9415, 2025. doi: 10.1080/07391102.2024.2442753. [Online]. Available: https://doi.org/10.1080/07391102.2024.2442753
  41. M. S. Çavuş, H. Yakan, H. Muğlu, and T. Bakır, "Novel carbohydrazones including 5-substituted isatin: Synthesis, characterization, and quantum-chemical studies on the relationship between electronic and antioxidant properties," J. Phys. Chem. Solids, vol. 140, p. 109362, May 2020. doi: 10.1016/j.jpcs.2020.109362. [Online]. Available: https://doi.org/10.1016/j.jpcs.2020.109362
  42. H. Muğlu, H. Yakan, and T. K. Bakır, "Synthesis, spectroscopic studies, and antioxidant activities of novel thio/carbohydrazones and bis-isatin derivatives from terephthalaldehyde," Turk. J. Chem., vol. 44, no. 2, pp. 237–248, Apr 2020. doi: 10.3906/kim-1910-13. [Online]. Available: https://doi.org/10.3906/kim-1910-13
  43. H. Muğlu, et al., "Preparation, antioxidant activity, and theoretical studies on the relationship between antioxidant and electronic properties of bis (thio/carbohydrazone) derivatives," J. Phys. Chem. Solids, vol. 164, p. 110618, May 2022. doi: 10.1016/j.jpcs.2022.110618. [Online]. Available: https://doi.org/10.1016/j.jpcs.2022.110618
  44. I. Fleming and D. Williams, Spectroscopic Methods in Organic Chemistry, 7th ed. Switzerland: Springer Nature, 2020. [Online]. Available: https://doi.org/10.1007/978-3-030-18252-6
  45. H. Muğlu, H. Yakan, A. G. A. Misbah, M. S. Çavuş, and T. K. Bakır, "Synthesis, structure characterization and quantum chemical study on relationship between structure and antioxidant properties of novel Schiff bases bearing (thio)/carbohydrazones," Res. Chem. Intermed., vol. 47, no. 12, pp. 4985–5005, Dec 2021. doi: 10.1007/s11164-021-04576-7. [Online]. Available: https://doi.org/10.1007/s11164-021-04576-7
  46. H. Muğlu, et al., "Exploring of antioxidant and antibacterial properties of novel 1, 3, 4-thiadiazole derivatives: Facile synthesis, structural elucidation and DFT approach to antioxidant characteristics," Comput. Biol. Chem., vol. 96, p. 107618, Feb 2022. doi: 10.1016/j.compbiolchem.2021.107618. [Online]. Available: https://doi.org/10.1016/j.compbiolchem.2021.107618
  47. F. Shahidi, "Antioxidants: Principles and applications," in Handbook of Antioxidants for Food Preservation. Elsevier, 2015, pp. 1–14. [Online]. Available: https://doi.org/10.1016/B978-1-78242-089-7.00001-4
  48. A. Božić et al., "Synthesis, antioxidant and antimicrobial activity of carbohydrazones," J. Serb. Chem. Soc., vol. 82, no. 5, pp. 495–508, May 2017. doi: 10.2298/JSC161220045B. [Online]. Available: https://doi.org/10.2298/JSC161220045B
  49. H. Muğlu, "Synthesis, characterization, and antioxidant activity of some new N4-arylsubstituted-5-methoxyisatin-β-thiosemicarbazone derivatives", Res. Chem. Intermed., vol. 46, no. 4, pp. 2083–2098, Apr 2020. doi: 10.1007/s11164-020-04079-x. [Online]. Available: https://doi.org/10.1007/s11164-020-04079-x
  50. H. Yakan, "Preparation, structure elucidation, and antioxidant activity of new bis (thiosemicarbazone) derivatives," Turk. J. Chem., vol. 44, no. 4, pp. 1085–1099, Aug 2020. doi: 10.3906/kim-2002-76. [Online]. Available: https://doi.org/10.3906/kim-2002-76
  51. H. Yakan, et al., "New 5-iodoisatin-thiosemicarbazones: preparation, spectroscopic characterization, antioxidant, urease inhibition activities, DFT studies, molecular docking, and molecular dynamic simulations," Res. Chem. Intermed., vol. 52, no. 1, pp. 631–661, Jan 2026. doi: 10.1007/s11164-025-05761-8. [Online]. Available: https://doi.org/10.1007/s11164-025-05761-8