Design, Synthesis and Evaluation of Pyrrol-thiazole Derivatives as AChE and BuChE Inhibitory and Antioxidant Activities

Ulviye Acar Çevik; Tugba Ercetin

doi:10.17776/csj.1255826

EN

Design, Synthesis and Evaluation of Pyrrol-thiazole Derivatives as AChE and BuChE Inhibitory and Antioxidant Activities

Abstract

Thiazole rings are one of the most frequently used heterocyclic moieties and are found in a wide variety of biologically active chemicals. In this research project, we report the synthesis and biological activities of some new thiazole derivatives (2a-2c) as potent anti-Alzheimer’s agents. These final compounds’ structures were characterized by spectral (1H NMR, 13C NMR, and MS spectra) analyses. The highest inhibitory activity against AChE was demonstrated by compound 2c (23.73 ± 0.018 %) with chloro substitution at the meta and para positions of the phenyl ring, while the highest inhibitory activity against BuChE was produced by compound 2a (28.87± 0.003 %) with cyano substitution at the f position of the phenyl ring. Ferrous ion-chelating and DPPH techniques were also used to assess the compounds' antioxidant properties. Compound 2a showed antioxidant effect according to the DPPH method with an IC50 value of 27.18 ± 0.009 µM.

Keywords

References

[1] Han C., Wei B.B., Shang P.P., Guo X.Y., Bai L.G., & Ma Z.Y., Design, synthesis and evaluation of 2-(2-oxoethyl) pyrimidine-5-carboxamide derivatives as acetylcholinesterase inhibitors, Bioorg. Med. Chem. Lett., 72 (2022) 128873.
[2] Messaad M., Dhouib I., Abdelhedi M., & Khemakhem B., Synthesis, bioassay and molecular docking of novel pyrazole and pyrazolone derivatives as acetylcholinesterase inhibitors, J. Mol. Struct., 1263 (2022) 133105.
[3] Mishra D., Fatima A., Kumar P., Munjal N.S., Singh B.K., Singh R., Synthesis of Benzothiazole Linked Triazole Conjugates and Their Evaluation Against Cholinesterase Enzymes, Chem. Select., 7 (2022) e202203060.
[4] Faghih Z., Khabnadideh S., Sakhteman A., Shirazi A.K., Yari H.A., Chatraei A., Rezaei Z., Sadeghian S., Synthesis, biological evaluation and molecular modeling studies of novel carbazole-benzylpiperazine hybrids as acetylcholinesterase and butyrylcholinesterase inhibitors, J. Mol. Struct., 1272 (2023) 134209.
[5] Aggarwal N., Jain S., Chopra N., Hybrids of thiazolidin-4-ones and 1, 3, 4-thiadiazole: Synthesis and biological screening of a potential new class of acetylcholinesterae inhibitors, Biointerface Res. Appl. Chem., 12 (2022) 2800-2812.
[6] Baréa P., dos Santos Yamazaki D.A., de Souza Lima D., Seixas F.A.V., da Costa W.F., de Freitas Gauze G., & Sarragiotto M.H., Design, synthesis, molecular docking and biological evaluation of β-carboline derivatives as cholinesterase inhibitors, J. Mol. Struct., 1273 (2023) 134291.
[7] Khan Y., Rehman W., Hussain R., Khan S., Malik A., Khan M., Liaqat A., Rasheed L., Begum F., Fazil S., Khan I., Abdellatif M.H., New biologically potent benzimidazole‐based‐triazole derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors along with molecular docking study, J. Heterocyc. Chem., 59 (2022) 2225-2239.
[8] Ullah H., Jabeen M., Rahim F., Hussain A., Khan F., Perviaz M., Sajid M., Uddin I., Khan M.U., Nabi M., Synthesis, acetylcholinesterase and butyrylcholinesterase inhibitory potential and molecular docking study of thiazole bearing thiourea analogues, Chem. Data Collect., 44 (2023) 100988.

[9] Zhou S., & Huang G., Synthesis and inhibitory activities of inhibitors for the treatment of Alzheimer’s disease, Chem. Biol. Drug Des., 99 (2022) 727-735.
[10] Silalai P., Jaipea S., Tocharus J., Athipornchai A., Suksamrarn A., & Saeeng R., New 1,2,3-Triazole-genipin Analogues and Their Anti-Alzheimer’s Activity, ACS omega., 7 (2022) 24302-24316.
[11] Khan S., Ullah H., Taha M., Rahim F., Sarfraz M., Iqbal R., Iqbal N., Hussain R., Shah S.A.A., Ayub K., Albalawi M.A., Abdelaziz M.A., Alatawi F.S., Khan K.M., Synthesis, DFT Studies, Molecular Docking and Biological Activity Evaluation of Thiazole-Sulfonamide Derivatives as Potent Alzheimer’s Inhibitors, Molecules, 28 (2023) 559.
[12] Hussain R., Ullah H., Rahim F., Sarfraz M., Taha M., Iqbal R., Rehman W., Khan S., Shah S.A.A., Hyder S., Alhomrani M., Alamri A.S., Abdulaziz O., Abdelaziz M.A., Multipotent Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease: Synthesis, Biological Analysis and Molecular Docking Study of Benzimidazole-Based Thiazole Derivatives, Molecules, 27 (2022) 6087.
[13] Kilic B., Bardakkaya M., Sagkan R. I., Aksakal F., Shakila S., & Dogruer D.S., New thiourea and benzamide derivatives of 2-aminothiazole as multi-target agents against Alzheimer's disease: Design, synthesis, and biological evaluation, Bioorg. Chem., 131 (2023) 106322.
[14] 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.
[15] 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.
[16] Ercetin T., Senol F.S., Orhan I.E. and 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.
[17] Blois M.S., Antioxidant determinations by the use of a stable free radical, Nature, 181 (1958) 1199-1200.
[18] Işık A., Çevik U.A., Celik I., Erçetin T., Koçak A., Özkay Y., & Kaplancıklı Z.A., Synthesis, characterization, molecular docking, dynamics simulations, and in silico absorption, distribution, metabolism, and excretion (ADME) studies of new thiazolylhydrazone derivatives as butyrylcholinesterase inhibitors, Z. Naturforsch. C., 77 (2022) 447-457.

Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences

Journal Section

Research Article

Authors

Ulviye Acar Çevik ^*
0000-0003-1879-1034
Türkiye

Tugba Ercetin
0000-0001-7774-7266
Türkiye

Publication Date

December 28, 2023

Submission Date

February 24, 2023

Acceptance Date

November 14, 2023

Published in Issue

Year 2023 Volume: 44 Number: 4

DOI

https://doi.org/10.17776/csj.1255826

IZ

https://izlik.org/JA38FN32UZ

Cite

RIS / Bibtex

APA

Acar Çevik, U., & Ercetin, T. (2023). Design, Synthesis and Evaluation of Pyrrol-thiazole Derivatives as AChE and BuChE Inhibitory and Antioxidant Activities. Cumhuriyet Science Journal, 44(4), 625-628. https://doi.org/10.17776/csj.1255826

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Recent Advancements in the Synthesis of Pyrazole Derivative for the Treatment of Alzheimer's Disease

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ChemistryOpen

https://doi.org/10.1002/open.202500305

Design, Synthesis and Evaluation of Pyrrol-thiazole Derivatives as AChE and BuChE Inhibitory and Antioxidant Activities

Abstract

Keywords

Öz

References

Details

Primary Language

Subjects

Journal Section

Authors

Publication Date

Submission Date

Acceptance Date

Published in Issue

DOI

IZ

Cite

Cited By

Recent Advancements in the Synthesis of Pyrazole Derivative for the Treatment of Alzheimer's Disease

Design, Synthesis, In Silico Absorption, Distribution, Metabolism, and Elimination and Molecular Docking Studies of Thiazole‐Based Furan Derivatives, and Their Biological Evaluation for Alzheimer Disease Therapy