Synthesis, Spectroscopic Studies and Antioxidant Activities of New 2-Benzylidene-N-Phenylhydrazine-1-Carbothioamide Derivatives
Year 2025,
Volume: 14 Issue: 3, 1704 - 1717, 30.09.2025
Temel Kan Bakır
,
Halit Muğlu
Abstract
Nowadays, thiosemicarbazone based schiff bases, which are the focus of attention due to their differential properties, are being synthesized in many studies and new aromatic structure added compounds are of significant interest in drug design and biochemistry. In this study, new thiosemicarbazide schiff bases containing different substituted groups were synthesized. The structure of new compound derivatives was characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), fourier transform infrared spectroscopy (FTIR) and elemental analyses. In addition, radical quenching capacities of newly synthesized compounds were investigated using 1,1-diphenyl-2-picryl hydrazyl (DPPH) method. IC50 values were calculated for the compounds and it was found that the antioxidant activities of the compounds changed in the order of 2>5>1>4>3. These results indicated that the presence of methoxy substituted groups that provide electrons to the aromatic ring structures of schiff bases would have positive effects on the antioxidant activities of the compounds.
Ethical Statement
The study is complied with research and publication ethics
References
-
H. P. Ebrahimi et al., “A novel series of thiosemicarbazone drugs: From synthesis to structure,” Spectrochim. Acta A Mol. Biomol. Spectrosc., vol. 137, pp. 1067–1077, 2015, doi: 10.1016/j.saa.2014.08.146.
-
D. Kovala-Demertzi, A. Boccarelli, M. A. Demertzis, and M. Coluccia, “In vitro antitumor activity of 2-acetyl pyridine 4N-ethyl thiosemicarbazone and its platinum(II) and palladium(II) complexes,” Chemotherapy, vol. 53, no. 2, pp. 148–152, 2007.
-
J. P. Scovill, D. L. Klayman, and C. F. Franchino, “2-acetylpyridine thiosemicarbazones. 4. Complexes with transition metals as antimalarial and antileukemic agents,” J. Med. Chem., vol. 25, no. 10, pp. 1261–1264, 1982.
-
W. Hernandez et al., “Synthesis, characterization, and in vitro cytotoxic activities of benzaldehyde thiosemicarbazone derivatives and their palladium(II) and platinum(II) complexes against various human tumor cell lines,” Bioinorg. Chem. Appl., vol. 2008, Art. no. 690952, 2008, doi: 10.1155/2008/690952.
-
H. Khan, “Synthesis, characterization and anticancer studies of mixed ligand dithiocarbamate palladium (II) complexes,” Eur. J. Med. Chem., vol. 46, pp. 4071–4077, 2011, doi: 10.1016/j.ejmech.2011.06.007.
-
V. F. S. Pape et al., “Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance,” Eur. J. Med. Chem., vol. 117, pp. 335–354, 2016.
-
P. King et al., “Bis(thiosemicarbazone) complexes of cobalt(III): Synthesis, characterization, and anticancer potential,” Inorg. Chem., vol. 56, pp. 6609–6623, 2017.
-
Gatti et al., “Half-sandwich arene ruthenium(II) and osmium(II) thiosemicarbazone complexes: Solution behavior and antiproliferative activity,” Organometallics, vol. 37, pp. 891–899, 2018.
-
P. Chellan et al., “Exploring the versatility of cycloplatinated thiosemicarbazones as antitumor and antiparasitic agents,” Organometallics, vol. 31, pp. 5791–5799, 2012.
-
Demoro et al., “New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: Potential anti-trypanosomal agents,” Dalton Trans., vol. 41, pp. 1534–1543, 2012, doi: 10.1039/c1dt11519g.
-
F. Vandresen et al., “Novel R-(+)-limonene-based thiosemicarbazones and their antitumor activity against human tumor cell lines,” Eur. J. Med. Chem., vol. 79, pp. 110–116, 2014, doi: 10.1016/j.ejmech.2014.03.086.
-
G. L. Parrilha et al., “Applications of radiocomplexes with thiosemicarbazones and bis(thiosemicarbazones) in diagnostic and therapeutic nuclear medicine,” Coord. Chem. Rev., vol. 458, 2022.
-
W.-x. Hu et al., “Synthesis and anticancer activity of thiosemicarbazones,” Bioorg. Med. Chem. Lett., vol. 16, pp. 2213–2218, 2006, doi: 10.1016/j.bmcl.2006.01.048.
-
J. Haribabu et al., “Isatin based thiosemicarbazone derivatives as potential bioactive agents: Anti-oxidant and molecular docking studies,” J. Mol. Struct., vol. 1110, pp. 185–195, 2016.
-
M. S. Çavuş, H. Yakan, C. Özorak, H. Muğlu, and T. K. Bakır, “New N,N′ bis(thioamido)thiocarbohydrazones and carbohydrazones: Synthesis, structure characterization, antioxidant activity, corrosion inhibitors and DFT studies,” Res. Chem. Intermed., vol. 48, pp. 1593–1613, 2022, doi: 10.1007/s11164-022-04659-z.
-
H. Hamedifar, S. Karimian, M. Kabiri, A. Bagheri, M. Zarei, A. Moazzam, M. Mahdavi, N. Sepehri, and M. Khoshneviszadeh, “Benzylidine-N-phenylhydrazine-1-carboxamide derivatives as tyrosinase inhibitors: Design, preparation, molecular docking, and biological activity,” ChemistrySelect, vol. 8, Art. no. e202300836, 2023, doi: 10.1002/slct.202300836.
-
Y. Demir et al., “Enzyme inhibition, molecular docking, and density functional theory studies of new thiosemicarbazones incorporating the 4-hydroxy-3,5-dimethoxy benzaldehyde motif,” Arch. Pharm. (Weinheim)., vol. 356, no. 4, p. e2200554, Apr. 2023, doi: 10.1002/ardp.202200554.
-
Huang, B. Ou, and L. Prior, “The chemistry behind antioxidant capacity assays,” J. Agric. Food Chem., vol. 53, no. 6, pp. 1841–1856, 2005, doi: 10.1021/jf030723c.
-
T. Bakır and J. B. Lawag, “Preparation, characterization, antioxidant properties of novel Schiff bases including 5-chloroisatin thiocarbohydrazone,” Res. Chem. Intermed., vol. 46, pp. 2541–2557, 2020, doi: 10.1007/s11164-020-04105-y.
-
N. Frankel and A. S. Meyer, “The problems of using one-dimensional methods to evaluate multifunctional food and biological antioxidants,” J. Sci. Food Agric., vol. 80, pp. 19–25, 2000.
-
W. Brand-Williams, M. E. Cuvelier, and C. Berset, “Use of a free radical method to evaluate antioxidant activity,” LWT - Food Sci. Technol., vol. 28, no. 1, pp. 25–30, 1995.
-
Q. ul-Ain, M. T. Muhammad, K. M. Khan, and M. I. Choudhary, “Estimation of in-vitro free radical scavenging and cytotoxic activities of thiocarbohydrazones derivatives,” arXiv, pp. 1–18, 2023, doi: 10.48550/arXiv.2310.00939.
-
C. Peyrot et al., “Bifunctional compounds targeting both D2 and non-α7 nACh receptors: Design, synthesis and pharmacological characterization,” Eur. J. Med. Chem., vol. 101, pp. 442–452, 2015.
-
B. Bakti and M. A. Martoprawiro, “Computational study of the effect of structure on antioxidant activity and drug score of coumarin derivatives,” Walisongo J. Chem., vol. 7, no. 2, pp. 181–192, 2024, doi: 10.21580/wjc.v7i2.23327.
-
P. Rajan et al., “Synthesis and evaluation of caffeic acid amides as antioxidants,” Bioorg. Med. Chem. Lett., vol. 11, pp. 215–217, 2001.
-
R. Gudipati, R. N. R. Anreddy, and S. Manda, “Synthesis, anticancer and antioxidant activities of some novel N-(benzo[d]oxazol-2-yl)-2-(7- or 5-substituted-2-oxoindolin-3-ylidene) hydrazinecarboxamide derivatives,” J. Enzyme Inhib. Med. Chem., vol. 26, no. 6, pp. 813–818, 2011, doi: 10.3109/14756366.2011.556630.
-
Studer, “A ‘Renaissance’ in radical trifluoromethylation,” Angew. Chem. Int. Ed., vol. 51, no. 36, pp. 8950–8958, Sep. 2012, doi: 10.1002/anie.201202624.
-
A. Rice-Evans, N. J. Miller, and G. Paganga, “Structure-antioxidant activity relationships of flavonoids and phenolic acids,” Free Radic. Biol. Med., vol. 20, no. 7, pp. 933–956, 1996, doi: 10.1016/0891-5849(95)02227-9.