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Potansiyel Antikolinesteraz Ajanlar Olarak Yeni İmidazol Türevlerinin Sentezi ve Karakterizasyonu

Year 2021, Volume: 16 Issue: 1, 301 - 307, 27.05.2021
https://doi.org/10.29233/sdufeffd.820955

Abstract

Alzheimer hastalığı en sık görülen nörodejeneratif hastalıklarıdan biridir. Gelişmiş ülkelerde %70-76 oranla görülen bu hastalığın radikal bir tedaviye sahip olmaması bilim dünyasını bu konu üzerinde çalışmaya yönlendirmektedir. Kolinerjik hipotez, AH hastalarında hafıza ve bilişsel bozukluğun ana nedeni düşük asetilkolin (ACh) düzeyinin olduğunu düşündürmektedir. Radikal bir tedavinin mevcut olmaması bilim insanları için bu alanı çekici kılmaktadır. İmidazol bileşikleri, çok çeşitli biyolojik aktiviteleri nedeniyle medisinal kimyada önemli bileşiklerdir. Bu çalışmada, yeni imidazol türevleri sentezlenmiş ve yapı tayinleri 1H-NMR, 13C-NMR ve kütle spektroskopisi metodları kullanılarak aydınlatılmıştır. Bileşiklerin aktivite profilleri in vitro Ellman metodu kullanılarak gerçekleştirilmiştir. Aktivite sonucunda elde edilen veriler, 6 ve 7 kodlu bileşiklerin antikolinesteraz aktivite profillerinin umut vaat edici olduğunu ortaya koymuştur.

Thanks

Bu çalışmanın yazarları olarak Anadolu Üniversitesi Eczacılık Fakültesi Doping ve Narkotik Maddeler Laboratuvarına destek ve katkılarından dolayı teşekkür ederiz.

References

  • [1] A. Mitelpunkt, T. Galili, T. Kozlovski, N. Bregman, N. Shachar, M. Markus-Kalish, Y. Benjamini, “Novel Alzheimer’s disease subtypes identified using a data and knowledge driven strategy,” Sci. Rep., 10(1), 1–13, 2020.
  • [2] M.L.B. Pulido, J.B.A. Hernández, M.A.F. Ballester, C.M.T. González, J. Mekyska, Z. Smékal “Alzheimer's disease and automatic speech analysis: a review,” Expert Syst. Appl., 113213, 2020.
  • [3] S. Cordone, L. De Gennaro, “Insights from human sleep research on neural mechanisms of Alzheimer’s disease,” Neural Regen. Res., 15(7), 1251, 2020.
  • [4] S. Singh, “Noradrenergic pathways of locus coeruleus in Parkinson’s and Alzheimer’s pathology,” Int. J. Neurosci., 130(3), 251-261, 2020.
  • [5] C. Bellenguez, B. Grenier-Boley, J.C. Lambert, “Genetics of Alzheimer’s disease: where we are, and where we are going,” Curr. Opin. Neurol., 61, 40-48, 2020.
  • [6] Y. Xu, Z. Zhang, X. Jiang, X. Chen, Z. Wang, H. Alsulami, W. “Tang. Discovery of δ-sultone-fused pyrazoles for treating Alzheimer's disease: Design, synthesis, biological evaluation and SAR studies,” Eur. J. Med. Chem., 181, 111598, 2019.
  • [7] P. Bai, K. Wang, P. Zhang, J. Shi, X. Cheng, Q. Zhang, Z. Sang, “Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease,”Eur. J. Med. Chem., 183, 111737, 2019.
  • [8] Ö. Keskin, “İmidazolidin-2-tiyon türevlerinin sentezi, karakterizasyonu, dft ve doking hesaplamaları,” Yüksek Lisans Tezi, Türkiye, Adıyaman Üniversitesi, Adıyaman, 2018.
  • [9] Wang, R. Shi, H. F. Zhao, J. F. He, Y. P. Zhang, H. B. Liu, J. P. ‘’Design, synthesis and aromatase inhibitory activities of novel indole-imidazole derivatives.’’ Bioorg. Med. Chem. Lett., 23(6), 1760-1762, 2013.
  • [10] Di Matteo, M. Ammazzalorso, A. Andreoli, F. Caffa, I. De Filippis, B. Fantacuzzi, M., Soncini, D. ‘’Synthesis and biological characterization of 3-(imidazol-1-ylmethyl) piperidine sulfonamides as aromatase inhibitors,’’ Bioorg. Med. Chem. Lett., 26(13), 3192-3194, 2016.
  • [11] Al-Wabli, R. I. Al-Ghamdi, A. R. Aswathy, S. A. V. Ghabbour, H. A. Al-Agamy, M. H. Hubert Joe, I. Attia, M. I. ‘’(2E)-2-[1-(1, 3-Benzodioxol-5-yl)-3-(1H-imidazol-1-yl) propylidene]-N-(2-chlorophenyl) hydrazine carboxamide: Synthesis, X-ray Structure, Hirshfeld Surface Analysis, DFT Calculations, Molecular Docking and Antifungal Profile,’’ Crystals, 9(2), 82, 2019.
  • [12] Vitorović-Todorović, M. D. Koukoulitsa, C. Juranić, I. O. Mandić, L. M., Drakulić, B. J. ‘’Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl-and butyrylcholinesterase inhibitory activity. Investigation of AChE–ligand interactions by docking calculations and molecular dynamics simulations,’’ Eur. J. Med. Chem., 81, 158-175, 2014.
  • [13] Xu, Y. X. Wang, H. Li, X. K. Dong, S. N. Liu, W. W. Gong, Q. ... Mao, F. ‘’Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted pyrimidinylthiourea derivatives as multifunctional agents for the treatment of Alzheimer's disease’’ Eur. J. Med. Chem., 143, 33-47, 2018.
  • [14] Lombardino JG. U.S. Patent No. 3,707,475. Washington, DC: U.S. Patent and Trademark Office 1972.
  • [15] G.L. Ellman, K.D. Courtney, Jr. V. Andres, R.M. Featherstone, “A new and rapid colorimetric determination of acetylcholinesterase activity,” Biochem. Pharmacol., 7, 88-95, 1961.
  • [16] U. Acar Çevik, B.N. Saglık, S. Levent, D. Osmaniye, B. Kaya Çavusoglu, Y. Özkay, Z.A. Kaplancıklı, “Synthesis and AChE-inhibitory activity of new benzimidazole derivatives,” Molecules, 24, 861, 2019.
  • [17] D. Osmaniye, B.N. Sağlık, U. Acar Çevik, S. Levent, B. Kaya Çavuşoğlu, Y. Özkay, G. Turan, “Synthesis and AChE inhibitory activity of novel thiazolylhydrazone derivatives,” Molecules, 24(13), 2392, 2019.

Synthesis and Characterization of New Imidazole Derivatives as Potential Anticholinesterase Agents

Year 2021, Volume: 16 Issue: 1, 301 - 307, 27.05.2021
https://doi.org/10.29233/sdufeffd.820955

Abstract

Alzheimer's disease is one of the most common neurodegenerative diseases. This disease, which is seen with a rate of 70-76% in developed countries, does not have a radical treatment, which directs the scientific world to work on this issue. The cholinergic hypothesis suggests that low acetylcholine (ACh) levels are the main cause of memory and cognitive impairment in AD patients. The absence of a radical treatment makes this area attractive for scientists. Imidazole compounds are important compounds in medicinal chemistry due to their wide variety of biological activities. In this study, new imidazole derivatives were synthesized and the structure determinations were elucidated using 1H-NMR, 13C-NMR and mass spectroscopy methods. The activity profiles of the compounds were performed using the in vitro Elisa method. The data obtained as a result of the activity showed that the anticholinesterase activity profiles of the 6 and 7 coded compounds were promising.

References

  • [1] A. Mitelpunkt, T. Galili, T. Kozlovski, N. Bregman, N. Shachar, M. Markus-Kalish, Y. Benjamini, “Novel Alzheimer’s disease subtypes identified using a data and knowledge driven strategy,” Sci. Rep., 10(1), 1–13, 2020.
  • [2] M.L.B. Pulido, J.B.A. Hernández, M.A.F. Ballester, C.M.T. González, J. Mekyska, Z. Smékal “Alzheimer's disease and automatic speech analysis: a review,” Expert Syst. Appl., 113213, 2020.
  • [3] S. Cordone, L. De Gennaro, “Insights from human sleep research on neural mechanisms of Alzheimer’s disease,” Neural Regen. Res., 15(7), 1251, 2020.
  • [4] S. Singh, “Noradrenergic pathways of locus coeruleus in Parkinson’s and Alzheimer’s pathology,” Int. J. Neurosci., 130(3), 251-261, 2020.
  • [5] C. Bellenguez, B. Grenier-Boley, J.C. Lambert, “Genetics of Alzheimer’s disease: where we are, and where we are going,” Curr. Opin. Neurol., 61, 40-48, 2020.
  • [6] Y. Xu, Z. Zhang, X. Jiang, X. Chen, Z. Wang, H. Alsulami, W. “Tang. Discovery of δ-sultone-fused pyrazoles for treating Alzheimer's disease: Design, synthesis, biological evaluation and SAR studies,” Eur. J. Med. Chem., 181, 111598, 2019.
  • [7] P. Bai, K. Wang, P. Zhang, J. Shi, X. Cheng, Q. Zhang, Z. Sang, “Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease,”Eur. J. Med. Chem., 183, 111737, 2019.
  • [8] Ö. Keskin, “İmidazolidin-2-tiyon türevlerinin sentezi, karakterizasyonu, dft ve doking hesaplamaları,” Yüksek Lisans Tezi, Türkiye, Adıyaman Üniversitesi, Adıyaman, 2018.
  • [9] Wang, R. Shi, H. F. Zhao, J. F. He, Y. P. Zhang, H. B. Liu, J. P. ‘’Design, synthesis and aromatase inhibitory activities of novel indole-imidazole derivatives.’’ Bioorg. Med. Chem. Lett., 23(6), 1760-1762, 2013.
  • [10] Di Matteo, M. Ammazzalorso, A. Andreoli, F. Caffa, I. De Filippis, B. Fantacuzzi, M., Soncini, D. ‘’Synthesis and biological characterization of 3-(imidazol-1-ylmethyl) piperidine sulfonamides as aromatase inhibitors,’’ Bioorg. Med. Chem. Lett., 26(13), 3192-3194, 2016.
  • [11] Al-Wabli, R. I. Al-Ghamdi, A. R. Aswathy, S. A. V. Ghabbour, H. A. Al-Agamy, M. H. Hubert Joe, I. Attia, M. I. ‘’(2E)-2-[1-(1, 3-Benzodioxol-5-yl)-3-(1H-imidazol-1-yl) propylidene]-N-(2-chlorophenyl) hydrazine carboxamide: Synthesis, X-ray Structure, Hirshfeld Surface Analysis, DFT Calculations, Molecular Docking and Antifungal Profile,’’ Crystals, 9(2), 82, 2019.
  • [12] Vitorović-Todorović, M. D. Koukoulitsa, C. Juranić, I. O. Mandić, L. M., Drakulić, B. J. ‘’Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl-and butyrylcholinesterase inhibitory activity. Investigation of AChE–ligand interactions by docking calculations and molecular dynamics simulations,’’ Eur. J. Med. Chem., 81, 158-175, 2014.
  • [13] Xu, Y. X. Wang, H. Li, X. K. Dong, S. N. Liu, W. W. Gong, Q. ... Mao, F. ‘’Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted pyrimidinylthiourea derivatives as multifunctional agents for the treatment of Alzheimer's disease’’ Eur. J. Med. Chem., 143, 33-47, 2018.
  • [14] Lombardino JG. U.S. Patent No. 3,707,475. Washington, DC: U.S. Patent and Trademark Office 1972.
  • [15] G.L. Ellman, K.D. Courtney, Jr. V. Andres, R.M. Featherstone, “A new and rapid colorimetric determination of acetylcholinesterase activity,” Biochem. Pharmacol., 7, 88-95, 1961.
  • [16] U. Acar Çevik, B.N. Saglık, S. Levent, D. Osmaniye, B. Kaya Çavusoglu, Y. Özkay, Z.A. Kaplancıklı, “Synthesis and AChE-inhibitory activity of new benzimidazole derivatives,” Molecules, 24, 861, 2019.
  • [17] D. Osmaniye, B.N. Sağlık, U. Acar Çevik, S. Levent, B. Kaya Çavuşoğlu, Y. Özkay, G. Turan, “Synthesis and AChE inhibitory activity of novel thiazolylhydrazone derivatives,” Molecules, 24(13), 2392, 2019.
There are 17 citations in total.

Details

Primary Language Turkish
Subjects Structural Biology, Chemical Engineering
Journal Section Makaleler
Authors

Derya Osmaniye 0000-0002-0499-436X

Betül Kaya Çavuşoğlu 0000-0001-8270-4949

Publication Date May 27, 2021
Published in Issue Year 2021 Volume: 16 Issue: 1

Cite

IEEE D. Osmaniye and B. Kaya Çavuşoğlu, “Potansiyel Antikolinesteraz Ajanlar Olarak Yeni İmidazol Türevlerinin Sentezi ve Karakterizasyonu”, Süleyman Demirel University Faculty of Arts and Science Journal of Science, vol. 16, no. 1, pp. 301–307, 2021, doi: 10.29233/sdufeffd.820955.