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Design, Synthesis and Cholinesterase Inhibitory Activity of Novel 1,3,4-Thiadiazole Derivatives

Year 2024, Volume: 45 Issue: 3, 503 - 509, 30.09.2024

Betül Kaya , Ulviye Acar Çevik , Bilge Çiftci , Mesut Isık , Zafer Asım Kaplancıklı , Şükrü Beydemir

https://doi.org/10.17776/csj.1449622

Abstract

Inhibition of the cholinesterases (AChE and BChE) plays a pivotal role in the symptomatic treatment of Alzheimer’s disease. The present study reports the synthesis and anticholinesterase activity of five novel thiadiazole analogs in search of anti-Alzheimer agents. The structures of the newly synthesized compounds were characterized using 1H NMR, 13C NMR and HRMS. Tested compounds inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes with IC50 values in the range of 8.250-20.382 μM and 14.143-0.986 μM, respectively. N-(4-Chlorophenyl)-2-[(5-(allylamino)-1,3,4-thiadiazol-2-yl)thio]-N-(3-nitrobenzyl)acetamide (6e) was determined as the most potent inhibitor against both tested enzymes when compared with standard drug tacrine. Molecular docking study was carried out to reveal the binding interactions between compound 6e and the active site of AChE

Keywords

Acetylcholinesterase Butyrylcholinesterase Cholinesterase inhibitors 1 3 4-thiadiazole Alzheimer’s disease

References

  • [1] Gauthier S., José P.R.-N., Morais A., Webster C., World Alzheimer Report 2021: Journey Through the Diagnosis of Dementia, (2021).
  • [2] Giacobini E., Cholinesterases: New Roles in Brain Function and in Alzheimer’s Disease, Neurochem. Res., 28 (2003) 515–522.
  • [3] Bala M., Ankalgi, A., Piplani P., Design, Synthesis and Pharmacological Evaluation of Disubstituted 1, 3, 4 Thiadiazoles Derivatives for The Treatment of Cognitive Dysfunction, J. Mol. Struct., 1291 (2023) 135951.
  • [4] Sharma D., Bansal K.K., Sharma A., Pathak M., Sharma P.C., A Brief Literature and Review of Patents on Thiazole-Related Derivatives, Curr. Bioact. Compd., 15 (2019) 304–315.
  • [5] Skrzypek A., Matysiak J., Niewiadomy A., Bajda M., Szymański, P., Synthesis and Biological Evaluation of 1, 3, 4-Thiadiazole Analogues as Novel AChE and BChE Inhibitors, Eur. J. Med. Chem., 62 (2013) 311-319.
  • [6] Atmaram U.A., Roopan S.M., Biological Activity of Oxadiazole and Thiadiazole Derivatives, Appl. Microbiol., 106 (2022) 3489-3505.
  • [7] Sharma B., Verma A., Prajapati S., Sharma U.K., Synthetic Methods, Chemistry, and the Anticonvulsant Activity of Thiadiazoles, Int. J. Med. Chem., 2013 (2013) 348948.
  • [8] Hatami M., Basri Z., Sakhvidi B.K., Mortazavi M., Thiadiazole–A Promising Structure in Design and Development of Anti-Alzheimer Agents, Int. Immunopharmacol., 118 (2023) 110027.
  • [9] Serban, G., Future Prospects in The Treatment of Parasitic Diseases: 2-Amino-1, 3, 4-Thiadiazoles in Leishmaniasis, Molecules, 24 (2019) 1557.
  • [10] 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., 12 (2018) 1545-1566.
  • [11] Talath S, Gadad AK., Synthesis, Antibacterial and Antitubercular Activities of Some 7-[4-(5-Amino-[1,3,4]thiadiazole-2-sulfonyl)-piperazin-1-yl]fluoroquinolonic Derivatives, Eur. J. Med. Chem., 41 (2006) 918–924.
  • [12] Serban G., 2-Amino-1,3,4-thiadiazoles as Prospective Agents in Trypanosomiasis and Other Parasitoses, Acta Pharm., 70 (2020) 259–290.
  • [13] Clerici F., Pocar D., Guido M., Loche A., Perlini V., Brufani M., Synthesis of 2-Amino-5-sulfanyl-1,3,4-thiadiazole Derivatives and Evaluation of Their Antidepressant and Anxiolytic Activity, J. Med. Chem., 44 (2001) 931–936.
  • [14] Çevik U.A., Osmaniye D., Levent S., Sağlik B. N., Çavuşoğlu B. K., Özkay Y., Kaplanciklı Z.A., Synthesis and Characterization of A New Series of Thiadiazole Derivatives as Potential Anticancer Agents, Heterocycl. Commun., 26 (2020) 6-13.
  • [15] Al-Sharabi A.A., Evren A.E., Sağlık B.N., Yurttaş L., Synthesis, Characterization, Molecular Docking and Molecular Dynamics Simulations of Novel 2, 5-Disubstituted-1, 3, 4-Thiadiazole Derivatives as Potential Cholinesterase/Monoamine Oxidase Dual Inhibitors for Alzheimer’s Disease, J. Biomol. Struct. Dyn, (2023) 1-19.
  • [16] Obakachi V.A., Kushwaha B., Kushwaha N.D., Mokoena S., Ganai A.M., Pathan T.K., Karpoormath R., Synthetic and Anticancer Activity Aspects of 1, 3, 4-Thiadiazole Containing Bioactive Molecules: A Concise Review, J. Sulphur Chem., 42 (2021) 670-691.
  • [17] Kaya B., Sağlık B.N., Levent S., Özkay Y., Kaplancıklı, Z.A., Synthesis of Some Novel 2-Substituted Benzothiazole Derivatives Containing Benzylamine Moiety as Monoamine Oxidase Inhibitory Agents, J. Enzyme Inhib. Med. Chem., 31 (2016), 1654-1661.
  • [18] Sağlık B.N., Çavuşoğlu B.K., Çevik U.A., Osmaniye D., Levent S., Özkay Y., Kaplancıklı Z.A. Novel 1, 3, 4-thiadiazole compounds as potential MAO-A inhibitors–design, synthesis, biological evaluation and molecular modelling, RSC Med. Chem., 11 (2020) 1063-1074.
  • [19] Ellman G. L., Courtney K. D., Andres Jr V., Featherstone, R. M., A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity, Biochem. Pharmacol., 7(2) (1961) 88-95.
  • [20] Mughal E. U., Sadiq A., Murtaza S., Rafique H., Zafar M. N., Riaz T., Khan B.A., Hameed A., Khan K. M., Synthesis, Structure–Activity Relationship and Molecular Docking Of 3-Oxoaurones And 3-Thioaurones As Acetylcholinesterase And Butyrylcholinesterase Inhibitors, Bioorg. Med. Chem., 25(1) (2017) 100-106.
  • [21] Işık M., Akocak S., Lolak N., Taslimi P., Türkeş C., Gülçin İ., Durgun M., Beydemir Ş., Synthesis, Characterization, Biological Evaluation, And in Silico Studies of Novel 1, 3‐Diaryltriazene‐Substituted Sulfathiazole Derivatives, Arch. Pharm., 353 (9) (2020) 2000102.
  • [22] Tarikoğulları A., Çizmecioğlu M., Saylam M., Parlar S., Alptüzün V., Soyer Z., Synthesis and Cholinesterase Inhibitory Activity of Some Phenylacetamide Derivatives Bearing 1H-Pyrazole or 1H-1, 2, 4-Triazole, Marmara Pharm. J., 20 (1) (2016) 21-27.
  • [23] Akocak S., Taslimi P., Lolak N., Işık M., Durgun M., Budak Y., Türkeş C., Gülçin İ., Beydemir Ş., Synthesis, Characterization, And Inhibition Study of Novel Substituted Phenylureido Sulfaguanidine Derivatives As α‐Glycosidase and Cholinesterase Inhibitors, Chem. Biodivers., 18 (4) (2021) e2000958.
  • [24] Durgun M., Türkeş C., Işık M., Demir Y., Saklı A., Kuru A., Güzel A., Beydemir Ş., Akocak S., Osman S.M., AlOthman Z., Supuran C. T., Synthesis, Characterisation, Biological Evaluation and In Silico Studies of Sulphonamide Schiff Bases, J. Enzyme Inhib. Med. Chem., 35 (1) (2020) 950-962.
  • [25] Akıncıoğlu A., Göksu S., Naderi A., Akıncıoğlu H., Kılınç N., Gülçin İ., Cholinesterases, Carbonic Anhydrase Inhibitory Properties and in Silico Studies of Novel Substituted Benzylamines Derived from Dihydrochalcones, Comput. Biol. Chem., 94 (2021) 107565.
  • [26] Alım Z., Şirinzade H., Kılınç N., Dilek E., Süzen S., Assessing Indole Derivative Molecules as Dual Acetylcholinesterase and Butyrylcholinesterase Inhibitors through in vitro Inhibition and Molecular Modelling Studies, J. Mol. Struct., 1311 (2024) 138276.
  • [27] Gök N., Akıncıoğlu A., Erümit Binici E., Akıncıoğlu H., Kılınç N., Göksu S. Synthesis of Novel Sulfonamides with Anti‐Alzheimer and Antioxidant Capacities, Arch. Pharm., 354(7) (2021) 2000496.
  • [28] Schrödinger Release 2024-1: Maestro, Schrödinger, 2024 LLC, New York, NY.
  • [29] Sastry G.M., Adzhigirey M., Day T., Annabhimoju R., Sherman W., Protein and Ligand Preparation: Parameters, Protocols, and Influence on Virtual Screening Enrichments, J. Comput. Aided Mol. Des., 27 (3) (2013) 221-234.
  • [30] Shah S. A. A., Ashraf M., Rehman J., Saleem R. S. Z., Synthesis, in Vitro And in Silico Studies Of S-Alkylated 5-(4-Methoxyphenyl)-4-Phenyl-4H-1, 2, 4-Triazole-3-Thiols as Cholinesterase Inhibitors, Pak. J. Pharm. Sci., 31(6) (2018) 2697-2708.
  • [31] Taha M., Rahim F., Uddin N., Khan I. U., Iqbal N., Salahuddin M., Farooq R.K., Gollapalli M., Khan K.M., Zafar A., Exploring Indole-Based-Thiadiazole Derivatives as Potent Acetylcholinesterase and Butyrylcholinesterase Enzyme Inhibitors, Int. J. Biol. Macromol., 188 (2021) 1025-1036.
  • [32] Hussain R., Ashraf M., Khan S., Rahim F., Rehman W., Taha M., Sardar A., Khan Y., Khan I., Shah S. A.A., Molecular Modeling, Synthesis, and in vitro Acetylcholinesterase and Butyrylcholinesterase Inhibitory Activities of Novel Benzimidazole-Bearing Thiadiazole Derivatives, J. Mol. Struct., 1295 (2024) 136582.

Year 2024, Volume: 45 Issue: 3, 503 - 509, 30.09.2024

Betül Kaya , Ulviye Acar Çevik , Bilge Çiftci , Mesut Isık , Zafer Asım Kaplancıklı , Şükrü Beydemir

https://doi.org/10.17776/csj.1449622

Abstract

References

  • [1] Gauthier S., José P.R.-N., Morais A., Webster C., World Alzheimer Report 2021: Journey Through the Diagnosis of Dementia, (2021).
  • [2] Giacobini E., Cholinesterases: New Roles in Brain Function and in Alzheimer’s Disease, Neurochem. Res., 28 (2003) 515–522.
  • [3] Bala M., Ankalgi, A., Piplani P., Design, Synthesis and Pharmacological Evaluation of Disubstituted 1, 3, 4 Thiadiazoles Derivatives for The Treatment of Cognitive Dysfunction, J. Mol. Struct., 1291 (2023) 135951.
  • [4] Sharma D., Bansal K.K., Sharma A., Pathak M., Sharma P.C., A Brief Literature and Review of Patents on Thiazole-Related Derivatives, Curr. Bioact. Compd., 15 (2019) 304–315.
  • [5] Skrzypek A., Matysiak J., Niewiadomy A., Bajda M., Szymański, P., Synthesis and Biological Evaluation of 1, 3, 4-Thiadiazole Analogues as Novel AChE and BChE Inhibitors, Eur. J. Med. Chem., 62 (2013) 311-319.
  • [6] Atmaram U.A., Roopan S.M., Biological Activity of Oxadiazole and Thiadiazole Derivatives, Appl. Microbiol., 106 (2022) 3489-3505.
  • [7] Sharma B., Verma A., Prajapati S., Sharma U.K., Synthetic Methods, Chemistry, and the Anticonvulsant Activity of Thiadiazoles, Int. J. Med. Chem., 2013 (2013) 348948.
  • [8] Hatami M., Basri Z., Sakhvidi B.K., Mortazavi M., Thiadiazole–A Promising Structure in Design and Development of Anti-Alzheimer Agents, Int. Immunopharmacol., 118 (2023) 110027.
  • [9] Serban, G., Future Prospects in The Treatment of Parasitic Diseases: 2-Amino-1, 3, 4-Thiadiazoles in Leishmaniasis, Molecules, 24 (2019) 1557.
  • [10] 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., 12 (2018) 1545-1566.
  • [11] Talath S, Gadad AK., Synthesis, Antibacterial and Antitubercular Activities of Some 7-[4-(5-Amino-[1,3,4]thiadiazole-2-sulfonyl)-piperazin-1-yl]fluoroquinolonic Derivatives, Eur. J. Med. Chem., 41 (2006) 918–924.
  • [12] Serban G., 2-Amino-1,3,4-thiadiazoles as Prospective Agents in Trypanosomiasis and Other Parasitoses, Acta Pharm., 70 (2020) 259–290.
  • [13] Clerici F., Pocar D., Guido M., Loche A., Perlini V., Brufani M., Synthesis of 2-Amino-5-sulfanyl-1,3,4-thiadiazole Derivatives and Evaluation of Their Antidepressant and Anxiolytic Activity, J. Med. Chem., 44 (2001) 931–936.
  • [14] Çevik U.A., Osmaniye D., Levent S., Sağlik B. N., Çavuşoğlu B. K., Özkay Y., Kaplanciklı Z.A., Synthesis and Characterization of A New Series of Thiadiazole Derivatives as Potential Anticancer Agents, Heterocycl. Commun., 26 (2020) 6-13.
  • [15] Al-Sharabi A.A., Evren A.E., Sağlık B.N., Yurttaş L., Synthesis, Characterization, Molecular Docking and Molecular Dynamics Simulations of Novel 2, 5-Disubstituted-1, 3, 4-Thiadiazole Derivatives as Potential Cholinesterase/Monoamine Oxidase Dual Inhibitors for Alzheimer’s Disease, J. Biomol. Struct. Dyn, (2023) 1-19.
  • [16] Obakachi V.A., Kushwaha B., Kushwaha N.D., Mokoena S., Ganai A.M., Pathan T.K., Karpoormath R., Synthetic and Anticancer Activity Aspects of 1, 3, 4-Thiadiazole Containing Bioactive Molecules: A Concise Review, J. Sulphur Chem., 42 (2021) 670-691.
  • [17] Kaya B., Sağlık B.N., Levent S., Özkay Y., Kaplancıklı, Z.A., Synthesis of Some Novel 2-Substituted Benzothiazole Derivatives Containing Benzylamine Moiety as Monoamine Oxidase Inhibitory Agents, J. Enzyme Inhib. Med. Chem., 31 (2016), 1654-1661.
  • [18] Sağlık B.N., Çavuşoğlu B.K., Çevik U.A., Osmaniye D., Levent S., Özkay Y., Kaplancıklı Z.A. Novel 1, 3, 4-thiadiazole compounds as potential MAO-A inhibitors–design, synthesis, biological evaluation and molecular modelling, RSC Med. Chem., 11 (2020) 1063-1074.
  • [19] Ellman G. L., Courtney K. D., Andres Jr V., Featherstone, R. M., A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity, Biochem. Pharmacol., 7(2) (1961) 88-95.
  • [20] Mughal E. U., Sadiq A., Murtaza S., Rafique H., Zafar M. N., Riaz T., Khan B.A., Hameed A., Khan K. M., Synthesis, Structure–Activity Relationship and Molecular Docking Of 3-Oxoaurones And 3-Thioaurones As Acetylcholinesterase And Butyrylcholinesterase Inhibitors, Bioorg. Med. Chem., 25(1) (2017) 100-106.
  • [21] Işık M., Akocak S., Lolak N., Taslimi P., Türkeş C., Gülçin İ., Durgun M., Beydemir Ş., Synthesis, Characterization, Biological Evaluation, And in Silico Studies of Novel 1, 3‐Diaryltriazene‐Substituted Sulfathiazole Derivatives, Arch. Pharm., 353 (9) (2020) 2000102.
  • [22] Tarikoğulları A., Çizmecioğlu M., Saylam M., Parlar S., Alptüzün V., Soyer Z., Synthesis and Cholinesterase Inhibitory Activity of Some Phenylacetamide Derivatives Bearing 1H-Pyrazole or 1H-1, 2, 4-Triazole, Marmara Pharm. J., 20 (1) (2016) 21-27.
  • [23] Akocak S., Taslimi P., Lolak N., Işık M., Durgun M., Budak Y., Türkeş C., Gülçin İ., Beydemir Ş., Synthesis, Characterization, And Inhibition Study of Novel Substituted Phenylureido Sulfaguanidine Derivatives As α‐Glycosidase and Cholinesterase Inhibitors, Chem. Biodivers., 18 (4) (2021) e2000958.
  • [24] Durgun M., Türkeş C., Işık M., Demir Y., Saklı A., Kuru A., Güzel A., Beydemir Ş., Akocak S., Osman S.M., AlOthman Z., Supuran C. T., Synthesis, Characterisation, Biological Evaluation and In Silico Studies of Sulphonamide Schiff Bases, J. Enzyme Inhib. Med. Chem., 35 (1) (2020) 950-962.
  • [25] Akıncıoğlu A., Göksu S., Naderi A., Akıncıoğlu H., Kılınç N., Gülçin İ., Cholinesterases, Carbonic Anhydrase Inhibitory Properties and in Silico Studies of Novel Substituted Benzylamines Derived from Dihydrochalcones, Comput. Biol. Chem., 94 (2021) 107565.
  • [26] Alım Z., Şirinzade H., Kılınç N., Dilek E., Süzen S., Assessing Indole Derivative Molecules as Dual Acetylcholinesterase and Butyrylcholinesterase Inhibitors through in vitro Inhibition and Molecular Modelling Studies, J. Mol. Struct., 1311 (2024) 138276.
  • [27] Gök N., Akıncıoğlu A., Erümit Binici E., Akıncıoğlu H., Kılınç N., Göksu S. Synthesis of Novel Sulfonamides with Anti‐Alzheimer and Antioxidant Capacities, Arch. Pharm., 354(7) (2021) 2000496.
  • [28] Schrödinger Release 2024-1: Maestro, Schrödinger, 2024 LLC, New York, NY.
  • [29] Sastry G.M., Adzhigirey M., Day T., Annabhimoju R., Sherman W., Protein and Ligand Preparation: Parameters, Protocols, and Influence on Virtual Screening Enrichments, J. Comput. Aided Mol. Des., 27 (3) (2013) 221-234.
  • [30] Shah S. A. A., Ashraf M., Rehman J., Saleem R. S. Z., Synthesis, in Vitro And in Silico Studies Of S-Alkylated 5-(4-Methoxyphenyl)-4-Phenyl-4H-1, 2, 4-Triazole-3-Thiols as Cholinesterase Inhibitors, Pak. J. Pharm. Sci., 31(6) (2018) 2697-2708.
  • [31] Taha M., Rahim F., Uddin N., Khan I. U., Iqbal N., Salahuddin M., Farooq R.K., Gollapalli M., Khan K.M., Zafar A., Exploring Indole-Based-Thiadiazole Derivatives as Potent Acetylcholinesterase and Butyrylcholinesterase Enzyme Inhibitors, Int. J. Biol. Macromol., 188 (2021) 1025-1036.
  • [32] Hussain R., Ashraf M., Khan S., Rahim F., Rehman W., Taha M., Sardar A., Khan Y., Khan I., Shah S. A.A., Molecular Modeling, Synthesis, and in vitro Acetylcholinesterase and Butyrylcholinesterase Inhibitory Activities of Novel Benzimidazole-Bearing Thiadiazole Derivatives, J. Mol. Struct., 1295 (2024) 136582.
There are 32 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

Bilge Çiftci

Mesut Isık

Zafer Asım Kaplancıklı

Şükrü Beydemir

Publication Date September 30, 2024
Submission Date March 11, 2024
Acceptance Date July 22, 2024
Published in Issue Year 2024Volume: 45 Issue: 3

Cite

APA Kaya, B., Acar Çevik, U., Çiftci, B., Isık, M., et al. (2024). Design, Synthesis and Cholinesterase Inhibitory Activity of Novel 1,3,4-Thiadiazole Derivatives. Cumhuriyet Science Journal, 45(3), 503-509. https://doi.org/10.17776/csj.1449622
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