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Synthesis, Anticholinesterase and Antioxidant Activity of Thiosemicarbazone Derivatives

Year 2024, Volume: 45 Issue: 3, 519 - 523, 30.09.2024

Betül Kaya , Ulviye Acar Çevik , Abdüllatif Karakaya , Tugba Ercetin

https://doi.org/10.17776/csj.1438171

Abstract

In this research, we report the synthesis and evaluation of novel thiosemicarbazones as anti-Alzheimer’s agents. The structural clarification of the newly synthesized compounds was carried out by 1H NMR, 13C NMR, and MS analyses. According to the in vitro cholinesterase inhibition assay, compounds showed more inhibitory potential against AChE than BuChE. The in vitro antioxidant activity of the synthesized compounds was measured via two different methods. According to ferrous ion-chelating assay compound 2b demonstrated 5.26% activity when compared to BHT (2.57%). DPPH radical scavenging activity assay revealed that compound 2b showed the most potent antioxidant activity with an IC50 value of 43.91 ± 0.021μM. Among the synthesized compounds, compound 2b was found as the most potent antioxidant agent.

Keywords

Thiosemicarbazone AChE BuChE Antioxidant

References

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  • [4] Lobo V., Patil A., Phatak A., Chandra N., Free Radicals, Antioxidants and Functional Foods: Impact on Human Health, Pharmacogn. Rev., 4 (2010) 118-126.
  • [5] Mostafa Abd El-Aal H.A.H., Lipid Peroxidation, In: Angel C., (Eds). Lipid Peroxidation End-Products as a Key of Oxidative Stress: Effect of Antioxidant on Their Production and Transfer of Free Radicals, IntechOpen, (2012).
  • [6] Engwa G.A., Phytochemicals - Source of Antioxidants and Role in Disease Prevention, In: Asao T., Asaduzzaman Md, Free Radicals and The Role of Plant Phytochemicals as Antioxidants Against Oxidative Stress-Related Diseases. Phytochemicals: Source of Antioxidants and Role in Disease Prevention, BoD–Books on Demand, (2018) 49-74.
  • [7] Chaudhary P., Janmeda P., Docea A.O., Yeskaliyeva B., Abdull Razis A.F., Modu B., Calina D., Sharifi-Rad, J., Oxidative Stress, Free Radicals and Antioxidants: Potential Crosstalk in the Pathophysiology of Human Diseases, Front. Chem., 11, (2023) 1158198.
  • [8] Batty M., Bennett M. R., Yu E., The Role of Oxidative Stress in Atherosclerosis, Cells, 11 (2022), 3843-3863.
  • [9] Sosa V., Moliné T., Somoza R., Paciucci R., Kondoh H., LLeonart M.E., Oxidative Stress and Cancer: An Overview, Ageing Res. Rev., 12 (2013) 376-390.
  • [10] Quiñonez-Flores C.M., González-Chávez S.A., Del Río Nájera D., Pacheco-Tena C., Oxidative Stress Relevance in The Pathogenesis of The Rheumatoid Arthritis: A Systematic Review, Biomed Res. Int., 2016 (2016) Article ID 6097417-6097431.
  • [11] Lee J.S., Kim H.G., Lee D.S., Son C.G., Oxidative Stress Is a Convincing Contributor to Idiopathic Chronic Fatigue, Sci. Rep., 8 (2018) 12890-12897.
  • [12] Huang W.J., Zhang X.I.A., Chen W.W., Role of Oxidative Stress in Alzheimer's Disease, Biomed. Rep., 4 (2016) 519-522.
  • [13] Dias V., Junn E., Mouradian M.M., The Role of Oxidative Stress in Parkinson's Disease, J. Parkinsons Dis., 3 (2013) 461-491.
  • [14] Kumar A., Ratan R.R., Oxidative Stress and Huntington’s disease: The good, the bad, and the ugly, J. Huntington's Dis., 5 (2016) 217-237.
  • [15] Hemerková P., Vališ M., Role of Oxidative Stress in the Pathogenesis of Amyotrophic Lateral Sclerosis: Antioxidant Metalloenzymes and Therapeutic Strategies, Biomolecules, 11 (2021) 437-460.
  • [16] Adamczyk B., Adamczyk-Sowa M., New Insights into The Role of Oxidative Stress Mechanisms in The Pathophysiology And Treatment of Multiple Sclerosis, Oxid. Med. Cell. Longev., 2016 (2016) Article ID 1973834.
  • [17] Zhang X., Fu Z., Meng L., He M., Zhang Z., The Early Events That Initiate β-amyloid Aggregation in Alzheimer’s Disease. Front. Aging Neurosci., 10 (2018) 359-369.
  • [18] Liu P.P., Xie Y., Meng X.Y., Kang J.S., History and Progress of Hypotheses and Clinical Trials for Alzheimer’s Disease, Signal Transduct. Target Ther., 4 (2019) 29-51.
  • [19] Agarwal M., Alam M.R., Haider M.K., Malik M.Z., Kim D.K., Alzheimer’s Disease: An Overview of Major Hypotheses and Therapeutic Options in Nanotechnology, Nanomaterials, 11 (2021) 59-77.
  • [20] Karakaya A., Maryam Z., Erçetin T., Çevik U.A., Synthesis of Thiazole Derivatives as Cholinesterase Inhibitors with Antioxidant Activity, Eur. J. Life Sci., 2 (2023) 118-124.
  • [21] Kovacevic Z., Kalinowski D.S., Lovejoy D.B., Yu Y., Suryo Rahmanto Y., Sharpe P.C., Bernhardt P.V., Richardson D.R., The medicinal Chemistry of Novel Iron Chelators for The Treatment of Cancer. Curr. Top. Med. Chem., 11 (2011) 483-499.
  • [22] Yu Y., Kalinowski D.S., Kovacevic Z., Siafakas A.R., Jansson P.J., Stefani C., Lovejoy D.B., Sharpe P.C., Bernhardt P.V., Richardson D.R., Thiosemicarbazones from The Old to New: Iron Chelators That Are More Than Just Ribonucleotide Reductase Inhibitors., J. Med. Chem., 52 (2009) 5271- 5294.
  • [23] Fasae K.D., Abolaji A. O., Faloye T.R., Odunsi A.Y., Oyetayo B.O., Enya J.I., Rotimi J.A., Akinyemi R.O., Whitworth A.J., Aschner, M., Metallobiology and Therapeutic Chelation of Biometals (Copper, Zinc and Iron) In Alzheimer’s Disease: Limitations, And Current and Future Perspectives, J. Trace Elem. Med. Biol., 67 (2021) 126779-126800.
  • [24] Koçyiğit Ü.M., Doğan M., Muğlu H., Taslimi P., Tüzün B., Yakan H., Bal H., Güzel E., Gülçin, İ., Determination of Biological Studies and Molecular Docking Calculations of Isatin-Thiosemicarbazone Hybrid Compounds, J. Mol. Struct., 1264 (2022) 133249.
  • [25] Palanimuthu D., Poon R., Sahni S., Anjum R., Hibbs D., Lin H. Y., Bernhardt P.V., Kalinowski D.S., Richardson, D.R., A Novel Class of Thiosemicarbazones Show Multi-Functional Activity for The Treatment of Alzheimer's Disease, Eur. J. Med. Chem., 139 (2017) 612-632.
  • [26] Yakan, H., Preparation, Structure Elucidation, And Antioxidant Activity of New Bis (Thiosemicarbazone) Derivatives, Turk. J. Chem., 44 (2020) 1085-1099.
  • [27] Zaib S., Munir R., Younas M.T., Kausar N., Ibrar A., Aqsa S., Shahid N., Asif T.T., Alsaab H.O., Khan, I., Hybrid Quinoline-Thiosemicarbazone Therapeutics as A New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis, Molecules, 26 (2021) 6573-6596.
  • [28] Nguyen D.T., Le TH., Bui T.T.T., Antioxidant Activities of Thiosemicarbazones from Substituted Benzaldehydes And N-(Tetra-O-Acetyl-Β-D-Galactopyranosyl) Thiosemicarbazide, Eur. J. Med. Chem., 60 (2013) 199-207.
  • [29] Ellman G.L., Courtney K.D., Andres Jr V., Featherstone R.M., A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity, Biochem. Pharmacol., 7 (1961) 88-95.
  • [30] Chua M.T., Tung YT., Chang S.T., Antioxidant Activities of Ethanolic Extracts from The Twigs of Cinnamomum Osmophloeum, Bioresour. Technol., 99 (2008) 1918-1925.
  • [31] Dinis, T.C.P., Madeira, V.M.C., Almeida, L.M., Action of Phenolic Derivatives (Acetaminophen, Salicylate, And 5-Aminosalicylate) As Inhibitors of Membrane Lipid Peroxidation and Peroxyl Radical Scavengers, Arch. Biochem. Biophys., 315 (1994) 161–169.
  • [32] Ercetin T., Senol F.S., Orhan I.E. Toker G., Comparative Assessment of Antioxidant and Cholinesterase Inhibitory Properties of The Marigold Extracts from Calendula arvensis L. and Calendula officinalis L, Ind. Crops Prod., 36 (2012) 203-208.
  • [33] Blois M.S., Antioxidant Determinations by the Use of a Stable Free Radical, Nature, 181 (1958) 1199–1200.
  • [34] Kaya B., Özkay Y., Temel H.E., Kaplancıklı Z.A. Synthesis and Biological Evaluation of Novel Piperazine Containing Hydrazone Derivatives, J. Chem., 2016 (2016) 1-7, 5878410.
  • [35] Yakan H., Preparation, structure elucidation, and antioxidant activity of new bis (thiosemicarbazone) derivatives, Turk. J. Chem., 44 (2020) 1085-1099.

Year 2024, Volume: 45 Issue: 3, 519 - 523, 30.09.2024

Betül Kaya , Ulviye Acar Çevik , Abdüllatif Karakaya , Tugba Ercetin

https://doi.org/10.17776/csj.1438171

Abstract

References

  • [1] Sens L., Oliveira A.S.D., Mascarello A., Brighente I., Yunes R. A., Nunes R. J., Synthesis, Antioxidant Activity, Acetylcholinesterase Inhibition and Quantum Studies of Thiosemicarbazones, J. Braz. Chem. Soc., 29 (2018) 343-352.
  • [2] Phaniendra A., Jestadi D. B., Periyasamy L., Free radicals: Properties, Sources, Targets, and Their Implication in Various Diseases, Indian J. Clin. Biochem., 30 (2015) 11-26.
  • [3] Mukherji S.M., Singh S.P., Reaction Mechanism in Organic Chemistry (Revised Edition), Revised by: Singh S.P., Prakash Om, India, Laxmi Publications (2008).
  • [4] Lobo V., Patil A., Phatak A., Chandra N., Free Radicals, Antioxidants and Functional Foods: Impact on Human Health, Pharmacogn. Rev., 4 (2010) 118-126.
  • [5] Mostafa Abd El-Aal H.A.H., Lipid Peroxidation, In: Angel C., (Eds). Lipid Peroxidation End-Products as a Key of Oxidative Stress: Effect of Antioxidant on Their Production and Transfer of Free Radicals, IntechOpen, (2012).
  • [6] Engwa G.A., Phytochemicals - Source of Antioxidants and Role in Disease Prevention, In: Asao T., Asaduzzaman Md, Free Radicals and The Role of Plant Phytochemicals as Antioxidants Against Oxidative Stress-Related Diseases. Phytochemicals: Source of Antioxidants and Role in Disease Prevention, BoD–Books on Demand, (2018) 49-74.
  • [7] Chaudhary P., Janmeda P., Docea A.O., Yeskaliyeva B., Abdull Razis A.F., Modu B., Calina D., Sharifi-Rad, J., Oxidative Stress, Free Radicals and Antioxidants: Potential Crosstalk in the Pathophysiology of Human Diseases, Front. Chem., 11, (2023) 1158198.
  • [8] Batty M., Bennett M. R., Yu E., The Role of Oxidative Stress in Atherosclerosis, Cells, 11 (2022), 3843-3863.
  • [9] Sosa V., Moliné T., Somoza R., Paciucci R., Kondoh H., LLeonart M.E., Oxidative Stress and Cancer: An Overview, Ageing Res. Rev., 12 (2013) 376-390.
  • [10] Quiñonez-Flores C.M., González-Chávez S.A., Del Río Nájera D., Pacheco-Tena C., Oxidative Stress Relevance in The Pathogenesis of The Rheumatoid Arthritis: A Systematic Review, Biomed Res. Int., 2016 (2016) Article ID 6097417-6097431.
  • [11] Lee J.S., Kim H.G., Lee D.S., Son C.G., Oxidative Stress Is a Convincing Contributor to Idiopathic Chronic Fatigue, Sci. Rep., 8 (2018) 12890-12897.
  • [12] Huang W.J., Zhang X.I.A., Chen W.W., Role of Oxidative Stress in Alzheimer's Disease, Biomed. Rep., 4 (2016) 519-522.
  • [13] Dias V., Junn E., Mouradian M.M., The Role of Oxidative Stress in Parkinson's Disease, J. Parkinsons Dis., 3 (2013) 461-491.
  • [14] Kumar A., Ratan R.R., Oxidative Stress and Huntington’s disease: The good, the bad, and the ugly, J. Huntington's Dis., 5 (2016) 217-237.
  • [15] Hemerková P., Vališ M., Role of Oxidative Stress in the Pathogenesis of Amyotrophic Lateral Sclerosis: Antioxidant Metalloenzymes and Therapeutic Strategies, Biomolecules, 11 (2021) 437-460.
  • [16] Adamczyk B., Adamczyk-Sowa M., New Insights into The Role of Oxidative Stress Mechanisms in The Pathophysiology And Treatment of Multiple Sclerosis, Oxid. Med. Cell. Longev., 2016 (2016) Article ID 1973834.
  • [17] Zhang X., Fu Z., Meng L., He M., Zhang Z., The Early Events That Initiate β-amyloid Aggregation in Alzheimer’s Disease. Front. Aging Neurosci., 10 (2018) 359-369.
  • [18] Liu P.P., Xie Y., Meng X.Y., Kang J.S., History and Progress of Hypotheses and Clinical Trials for Alzheimer’s Disease, Signal Transduct. Target Ther., 4 (2019) 29-51.
  • [19] Agarwal M., Alam M.R., Haider M.K., Malik M.Z., Kim D.K., Alzheimer’s Disease: An Overview of Major Hypotheses and Therapeutic Options in Nanotechnology, Nanomaterials, 11 (2021) 59-77.
  • [20] Karakaya A., Maryam Z., Erçetin T., Çevik U.A., Synthesis of Thiazole Derivatives as Cholinesterase Inhibitors with Antioxidant Activity, Eur. J. Life Sci., 2 (2023) 118-124.
  • [21] Kovacevic Z., Kalinowski D.S., Lovejoy D.B., Yu Y., Suryo Rahmanto Y., Sharpe P.C., Bernhardt P.V., Richardson D.R., The medicinal Chemistry of Novel Iron Chelators for The Treatment of Cancer. Curr. Top. Med. Chem., 11 (2011) 483-499.
  • [22] Yu Y., Kalinowski D.S., Kovacevic Z., Siafakas A.R., Jansson P.J., Stefani C., Lovejoy D.B., Sharpe P.C., Bernhardt P.V., Richardson D.R., Thiosemicarbazones from The Old to New: Iron Chelators That Are More Than Just Ribonucleotide Reductase Inhibitors., J. Med. Chem., 52 (2009) 5271- 5294.
  • [23] Fasae K.D., Abolaji A. O., Faloye T.R., Odunsi A.Y., Oyetayo B.O., Enya J.I., Rotimi J.A., Akinyemi R.O., Whitworth A.J., Aschner, M., Metallobiology and Therapeutic Chelation of Biometals (Copper, Zinc and Iron) In Alzheimer’s Disease: Limitations, And Current and Future Perspectives, J. Trace Elem. Med. Biol., 67 (2021) 126779-126800.
  • [24] Koçyiğit Ü.M., Doğan M., Muğlu H., Taslimi P., Tüzün B., Yakan H., Bal H., Güzel E., Gülçin, İ., Determination of Biological Studies and Molecular Docking Calculations of Isatin-Thiosemicarbazone Hybrid Compounds, J. Mol. Struct., 1264 (2022) 133249.
  • [25] Palanimuthu D., Poon R., Sahni S., Anjum R., Hibbs D., Lin H. Y., Bernhardt P.V., Kalinowski D.S., Richardson, D.R., A Novel Class of Thiosemicarbazones Show Multi-Functional Activity for The Treatment of Alzheimer's Disease, Eur. J. Med. Chem., 139 (2017) 612-632.
  • [26] Yakan, H., Preparation, Structure Elucidation, And Antioxidant Activity of New Bis (Thiosemicarbazone) Derivatives, Turk. J. Chem., 44 (2020) 1085-1099.
  • [27] Zaib S., Munir R., Younas M.T., Kausar N., Ibrar A., Aqsa S., Shahid N., Asif T.T., Alsaab H.O., Khan, I., Hybrid Quinoline-Thiosemicarbazone Therapeutics as A New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis, Molecules, 26 (2021) 6573-6596.
  • [28] Nguyen D.T., Le TH., Bui T.T.T., Antioxidant Activities of Thiosemicarbazones from Substituted Benzaldehydes And N-(Tetra-O-Acetyl-Β-D-Galactopyranosyl) Thiosemicarbazide, Eur. J. Med. Chem., 60 (2013) 199-207.
  • [29] Ellman G.L., Courtney K.D., Andres Jr V., Featherstone R.M., A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity, Biochem. Pharmacol., 7 (1961) 88-95.
  • [30] Chua M.T., Tung YT., Chang S.T., Antioxidant Activities of Ethanolic Extracts from The Twigs of Cinnamomum Osmophloeum, Bioresour. Technol., 99 (2008) 1918-1925.
  • [31] Dinis, T.C.P., Madeira, V.M.C., Almeida, L.M., Action of Phenolic Derivatives (Acetaminophen, Salicylate, And 5-Aminosalicylate) As Inhibitors of Membrane Lipid Peroxidation and Peroxyl Radical Scavengers, Arch. Biochem. Biophys., 315 (1994) 161–169.
  • [32] Ercetin T., Senol F.S., Orhan I.E. Toker G., Comparative Assessment of Antioxidant and Cholinesterase Inhibitory Properties of The Marigold Extracts from Calendula arvensis L. and Calendula officinalis L, Ind. Crops Prod., 36 (2012) 203-208.
  • [33] Blois M.S., Antioxidant Determinations by the Use of a Stable Free Radical, Nature, 181 (1958) 1199–1200.
  • [34] Kaya B., Özkay Y., Temel H.E., Kaplancıklı Z.A. Synthesis and Biological Evaluation of Novel Piperazine Containing Hydrazone Derivatives, J. Chem., 2016 (2016) 1-7, 5878410.
  • [35] Yakan H., Preparation, structure elucidation, and antioxidant activity of new bis (thiosemicarbazone) derivatives, Turk. J. Chem., 44 (2020) 1085-1099.
There are 35 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Chemistry
Journal Section Natural Sciences
Authors

Betül Kaya 0000-0002-1713-9485

Ulviye Acar Çevik 0000-0003-1879-1034

Abdüllatif Karakaya 0009-0003-9619-6705

Tugba Ercetin 0000-0001-7774-7266

Publication Date September 30, 2024
Submission Date February 17, 2024
Acceptance Date July 22, 2024
Published in Issue Year 2024Volume: 45 Issue: 3

Cite

APA Kaya, B., Acar Çevik, U., Karakaya, A., Ercetin, T. (2024). Synthesis, Anticholinesterase and Antioxidant Activity of Thiosemicarbazone Derivatives. Cumhuriyet Science Journal, 45(3), 519-523. https://doi.org/10.17776/csj.1438171
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