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Novel 2,6-disubstituted-3-(2H)-pyridazones as Cholinesterase Inhibitors: In vitro Enzyme Inhibition and In silico Molecular Modelling and Dynamic Studies

Yıl 2022, Cilt: 4 Sayı: 2, 80 - 95, 31.08.2022

Azime Berna Özçelik Hasan Erkan Rüzgar Fatma Sezer Şenol Deniz İlkay Erdoğan Orhan Mehmet Abdullah Alagöz Zeynep Özdemir

Öz

The approach proposed as the cholinergic hypothesis for Alzheimer's Disease contributed significantly to the explanation of cognitive decline observed in the elderly and Alzheimer's patients due to dysfunction of neurons containing acetylcholine in the brain. To date, this notion has formed the basis of most of the treatment strategies and drug development approaches for Alzheimer Disease. Within the scope of this study, in which the synthesis and biological evaluation of pyridazinones, which are designed for multi-enzyme targets and expected to act as AChE and BChE inhibitors, were performed, 12 new compounds were synthesized, their in vitro enzyme inhibitor activities were evaluated and molecular modeling studies were carried out. While the compounds did not show significant AChE inhibition, they showed a high degree of BChE inhibition. D2e was determined as the most potent BChE inhibitor and molecular modeling and molecular dynamics simulation studies were also carried out for D2e and tacrine. The obtained results suggest that new pyridazinone derivatives can act as BChE inhibitory agents. Although the synthesized compounds are less effective than the reference drugs, it has been concluded that it is possible to reach the precursor compounds as a result of suitable modifications.

Anahtar Kelimeler

Alzheimer AChE BChE Pyridazinone Molecular docking

Destekleyen Kurum

Gazi Üniversitesi

Proje Numarası

02/2017-22

Teşekkür

This work was supported by Research Foundation of Gazi University (02/2017-22).

Kaynakça

  • Ahmed, E. M. , Hassan, M. S. , El-Malah, A. A., Kassab, A. E. (2020). New pyridazine derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents; design, synthesis and biological evaluation., Bioorganic Chemistry, 95, 103497. https://doi.org/10.1016/j.bioorg.2019.103497
  • Alagöz, M. A. , Özdemir, Z., Özçelik, A. B. (2019). Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases. International Journal of Pharmacy and Chemistry, 5(3), 26-30. https://doi.org/10.11648/j.ijpc.20190503.11 Anand, P. & P. Singh,P. (2013). A review on cholinesterase inhibitors for Alzheimer’s disease. Archives of Pharmacal Research, 36, 375-399. https://doi.org/10.1007/s12272-013-0036-3
  • Banerjee, P. S. (2011). Various Biological Activities of Pyridazinone Ring Derivatives. Asian Journal of Chemistry, 23, 1905-1910.
  • Bozbey, İ. , Özdemir, Z., Uslu, H. , Özçelik, A. B. , Şenol, F. S., Orhan-Erdoğan, İ., Uysal, M. (2020). A Series of New Hydrazone Derivatives: Synthesis, Molecular Docking and Anticholinesterase Activity Studies. Mini-Reviews in Medicinal Chemistry, 20(11), 1042-1060. https://doi.org/10.2174/1389557519666191010154444 Çeçen,M., Oh, J. M. , Özdemir, Z., Büyüktuncel, S. E. . Uysal, M., Abdelgawad, M. A. ,. Musa,A., Gambacorta, N., Nicolotti, O., Mathew, B. , Kim H. (2020). Design, Synthesis, and Biological Evaluation of Pyridazinones Containing the (2-Fluorophenyl) Piperazine Moiety as Selective MAO-B Inhibitors. Molecules, 25(22), 5371. https://doi.org/10.3390/molecules25225371
  • Chatonnet, A. & Lockridge, O. (1989). Comparison of butyrylcholinesterase and acetylcholinesterase. Biochemical Journal, 260(3), 625-634. https://doi.org/10.1042/bj2600625
  • Ciftci, O. , Özdemir, Z., Acar, C. , Sözen, M. , Basak-Türkmen, N., Ayhan, I., Gözükara, H. (2018). The Novel Synthesized Pyridazinone Derivates had the Antiproliferative and Apoptotic Effects in SHSY5Y and HEP3B Cancer Cell Line. Letters in Organic Chemistry, 15(4), 323-331. https://doi.org/10.2174/1570178614666170707154210
  • Costas-Lago, M. C. , Besada, P. , Rodrıguez-Enrıquez, F., Viña, D., Vilar, S., Uriarte, E., Borges, F. , Terán, C. (2017).Synthesis and structure-activity relationship study of novel 3-heteroarylcoumarins based on pyridazine scaffold as selective MAO-B inhibitors. European Journal of Medicinal Chemistry., 139, 1-11. https://doi.org/10.1016/j.ejmech.2017.07.045
  • Dvir, H., Silman, I., Harel, M., Rosenberry, T. L. , Sussmana, J. L. (2010). Acetylcholinesterase: from 3D structure to function. Chemico-Biological Interactions, 187, 10-22. https://doi.org/10.1016/j.cbi.2010.01.042
  • Ellman, G. L., Courtney, K. D., Andres Jr, V., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical pharmacology, 7(2), 88-95. https://doi.org/10.1016/0006-2952(61)90145-9
  • Hampel, H., Mesulam, M. M., Cuello, A. C., Farlow, M. R., Giacobini, E., Grossberg, G. T., Khachaturian,. Vergallo, A. S. A, Cavedo,E., Snyder, P. J.,. Khachaturian, Z. S. (2018). The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain, 141(7), 1917-1933. https://doi.org/10.1093/brain/awy132
  • Heo, H. J. , Kim, M. J. , Lee, J. M. , Choi, S. J. , Cho, H. Y. , Hong, B. , Kim, H. K. , Kim, E., Shin, D. H.. (2004). Naringenin from Citrus junos has an inhibitory effect on acetylcholinesterase and a mitigating effect on amnesia. Dementia and Geriatric Cognitive Disorders, 17, 151-157. https://doi.org/10.1159/000076349
  • Katritzky, A. R. & Lagowski, J. M. (1963). Prototropic Tautomerism of Heteroaromatic Compounds: I. General Discussion and Methods of Study. Advances in Heterocyclic Chemistry, 1, 311-338. https://doi.org/10.1016/S0065-2725(08)60528-0
  • Kilic, B., Gulcan, H. O. , Aksakal, F. (2018). Design and synthesis of some new carboxamide and propanamide derivatives bearing phenylpyridazine as a core ring and the investigation of their inhibitory potential on in-vitro acetylcholinesterase and butyrylcholinesterase. Bioorganic Chemistry, 79, 235-249. https://doi.org/10.1016/j.bioorg.2018.05.006
  • Lapinski, L., Nowak, M. J. , Fulara, J. , Les´, A., Adamowicz, L. (1992). Relation between structure and tautomerism in diazinones and diazinethlones. An experimental matrix isolation and theoretical ab initio study. The Journal of Physical Chemistry, 96, 6250–6254.
  • Orhan, S., Aslan, M.İ, Kartal, B.İ Şener, K. H. C. Başer, (2008). Inhibitory effect of Turkish Rosmarinus officinalis L. On acetylcholinesterase and butyrylcholinesterase enzymes. Food Chemistry, 108663-668. https://doi.org/10.1016/j.foodchem.2007.11.023
  • Özçelik, A. B., Özdemir, Z., Sari, S. , Utku, S. , Uysal, M. (2019). A New Series of Pyridazinone Derivatives as Cholinesterases Inhibitors: Synthesis, In Vitro Activity and Molecular Modeling Studies. Pharmacological Reports, 71(6), 1253-1263. https://doi.org/10.1016/j.pharep.2019.07.006
  • Özdemir, Z. , Yılmaz, H., Sarı, S., Karakurt, A., Şenol, F. S., Uysal, M. (2017). Design, synthesis, and molecular modeling of new 3(2H)-pyridazinone derivatives as acetylcholinesterase/butyrylcholinesterase inhibitors. Medicinal Chemistry Research, 26, 2293-2308. https://doi.org/10.1007/s00044-017-1930-x
  • Özdemir, Z., Başak-Türkmen, N., Ayhan, İ., Çiftçi, O.,M. Uysal, M. (2019). Synthesis of New 6-[4-(2-Fluorophenylpiperazine-1-yl)]-3(2H)-pyridazinone-2-acethyl-2-(substitutedbenzal)hydrazone Derivatives and Evulation of Their Cytotoxic Effects in Liver and Colon Cancer Cell Line. Pharmaceutical Chemistry Journal, 52;11, 952-959. https://doi.org/10.1007/s11094-019-01927-y Özdemir, Z.,. Alagöz, M. A. (2019). Anticholinesterases (Eds: I. J. Al-Zwaini, A. AL-Mayahi), Selected Topics in Myasthenia Gravis. 1st edition. London: Intech Open, 69-78. https://doi.org/10.2174/0929867328666210203204710
  • Özten, Ö. , Zengin Kurt, B., Sönmez, F., Doğan, B., Durdagi, S. (2021). Synthesis, molecular docking and molecular dynamics studies of novel tacrine-carbamate derivatives as potent cholinesterase inhibitors. Bioorganic Chemistry, 115105225. https://doi.org/10.1016/j.bioorg.2021.105225
  • Rathish, I. G., Javed, K. , Bano, S., Ahmad, S. ,. Alam, M. S., Pillai, K. K. (2009). Synthesis and blood glucose lowering effect of novel pyridazinone substituted benzenesulfonylurea derivatives. European Journal of Medicinal Chemistry, 44, 2673-2678. https://doi.org/10.1016/j.ejmech.2008.12.013
  • Roth, G. J. , Heckel, A., Kley, J. T. (2015). Design, synthesis and evaluation of MCH receptor 1 antagonists-Part II: optimization of pyridazines toward reduced phospholipidosis and hERG inhibition. Bioorganic & Medicinal Chemistry Letters, 25, 3270-3274. https://doi.org/10.1016/j.bmcl.2015.05.074
  • Sabt, A., Eldehna, W. M. , Al-Warhi, T. ,. Alotaibi, O. J., Elaasser, M. M. , Suliman, H., Abdel-Aziz, H. A. (2020). Discovery of 3,6- disubstituted pyridazines as a novel class of anticancer agents targeting cyclin-dependent kinase 2: synthesis, biological evaluation and in silico insights Journal of Enzyme Inhibition and Medicinal Chemistry, 35(1), 1616-1630. https://doi.org/10.1080/14756366.2020.1806259
  • Sameem, B., Saeedi,M., Mahdavi, M., Shafiee, A. (2018). A review on tacrine-based scaffolds as multi-target drugs (MTDLs) for Alzheimer's disease. European Journal of Medicinal Chemistry, 128(10), 332-345. https://doi.org/10.1016/j.ejmech.2016.10.060
  • Schmidt, P. , Druey, J. (1954). Heilmittelchemische Studien in der heterocyclischen Reihe. 10. Mitteilung. Pyridazine VII. Zur neuen Pyridazin-Synthese.Methylpyridazine. Helvetica Chimica Acta. 37(5), 1467-1471. https://doi.org/10.1002/HLCA.19540370514
  • Tan, O. U. , Ozadali, K. , Yogeeswari, P. (2012). Synthesis and antimycobacterial activities of some new N-acylhydrazone and thiosemicarbazide derivatives of 6-methyl-4,5-dihydropyridazin-3(2H)-one. Medicinal Chemistry Research, 21, 2388-2394. https://doi.org/10.1007/s00044-011-9770-6
  • Türkeş, C., Akocak, S. , Işık, M., Lolak, N., Taslimi, P., Durgun, M., Gülçin, İ. , Budak, Y. , Beydemir, Ş. (2021). Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitors. Journal of Biomolecular Structure and Dynamics, 40(5), 1-13. https://doi.org/10.1080/07391102.2021.1916599
  • Utku, I. , Gökçe, M., Aslan, G., Bayram, G. , Ülger, M., Emekdaş, G., Şahin, M. F. (2011). Synthesis and in vitro antimycobacterial activities of novel 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(substituted/nonsubstituted acetophenone) hydrazine. Arzneimittelforschung, 61(1), 1-7. https://doi.org/10.3906/kim-1009-63
  • Utku, S ., Gökçe, M., Orhan, İ., Şahin, M. F. (2011). Synthesis of novel 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(substituted/-nonsubstituted benzal)hydrazone derivatives and acetylcholinesterase and butyrylcholinesterase inhibitory activities in vitro. Journal of Chemistry, 829(35), 331-339. https://doi.org/10.1055/s-0031-1296161.
  • Yamali, C., Ozan, G. H. , Kahya, B., Çobanoğlu, S., Şüküroğlu, M. K., Doğruer, D. S. (2015). Synthesis of some 3(2H)-pyridazinone and 1(2H)-phthalazinone derivatives incorporating aminothiazole moiety and investigation of their antioxidant, acetylcholinesterase, and butyrylcholinesterase inhibitory activities. Medicinal Chemistry Research, 24, 1210-1217. https://doi.org/10.1007/s00044-014-1205-8

Yıl 2022, Cilt: 4 Sayı: 2, 80 - 95, 31.08.2022

Azime Berna Özçelik Hasan Erkan Rüzgar Fatma Sezer Şenol Deniz İlkay Erdoğan Orhan Mehmet Abdullah Alagöz Zeynep Özdemir

Öz

Proje Numarası

02/2017-22

Kaynakça

  • Ahmed, E. M. , Hassan, M. S. , El-Malah, A. A., Kassab, A. E. (2020). New pyridazine derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents; design, synthesis and biological evaluation., Bioorganic Chemistry, 95, 103497. https://doi.org/10.1016/j.bioorg.2019.103497
  • Alagöz, M. A. , Özdemir, Z., Özçelik, A. B. (2019). Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases. International Journal of Pharmacy and Chemistry, 5(3), 26-30. https://doi.org/10.11648/j.ijpc.20190503.11 Anand, P. & P. Singh,P. (2013). A review on cholinesterase inhibitors for Alzheimer’s disease. Archives of Pharmacal Research, 36, 375-399. https://doi.org/10.1007/s12272-013-0036-3
  • Banerjee, P. S. (2011). Various Biological Activities of Pyridazinone Ring Derivatives. Asian Journal of Chemistry, 23, 1905-1910.
  • Bozbey, İ. , Özdemir, Z., Uslu, H. , Özçelik, A. B. , Şenol, F. S., Orhan-Erdoğan, İ., Uysal, M. (2020). A Series of New Hydrazone Derivatives: Synthesis, Molecular Docking and Anticholinesterase Activity Studies. Mini-Reviews in Medicinal Chemistry, 20(11), 1042-1060. https://doi.org/10.2174/1389557519666191010154444 Çeçen,M., Oh, J. M. , Özdemir, Z., Büyüktuncel, S. E. . Uysal, M., Abdelgawad, M. A. ,. Musa,A., Gambacorta, N., Nicolotti, O., Mathew, B. , Kim H. (2020). Design, Synthesis, and Biological Evaluation of Pyridazinones Containing the (2-Fluorophenyl) Piperazine Moiety as Selective MAO-B Inhibitors. Molecules, 25(22), 5371. https://doi.org/10.3390/molecules25225371
  • Chatonnet, A. & Lockridge, O. (1989). Comparison of butyrylcholinesterase and acetylcholinesterase. Biochemical Journal, 260(3), 625-634. https://doi.org/10.1042/bj2600625
  • Ciftci, O. , Özdemir, Z., Acar, C. , Sözen, M. , Basak-Türkmen, N., Ayhan, I., Gözükara, H. (2018). The Novel Synthesized Pyridazinone Derivates had the Antiproliferative and Apoptotic Effects in SHSY5Y and HEP3B Cancer Cell Line. Letters in Organic Chemistry, 15(4), 323-331. https://doi.org/10.2174/1570178614666170707154210
  • Costas-Lago, M. C. , Besada, P. , Rodrıguez-Enrıquez, F., Viña, D., Vilar, S., Uriarte, E., Borges, F. , Terán, C. (2017).Synthesis and structure-activity relationship study of novel 3-heteroarylcoumarins based on pyridazine scaffold as selective MAO-B inhibitors. European Journal of Medicinal Chemistry., 139, 1-11. https://doi.org/10.1016/j.ejmech.2017.07.045
  • Dvir, H., Silman, I., Harel, M., Rosenberry, T. L. , Sussmana, J. L. (2010). Acetylcholinesterase: from 3D structure to function. Chemico-Biological Interactions, 187, 10-22. https://doi.org/10.1016/j.cbi.2010.01.042
  • Ellman, G. L., Courtney, K. D., Andres Jr, V., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical pharmacology, 7(2), 88-95. https://doi.org/10.1016/0006-2952(61)90145-9
  • Hampel, H., Mesulam, M. M., Cuello, A. C., Farlow, M. R., Giacobini, E., Grossberg, G. T., Khachaturian,. Vergallo, A. S. A, Cavedo,E., Snyder, P. J.,. Khachaturian, Z. S. (2018). The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain, 141(7), 1917-1933. https://doi.org/10.1093/brain/awy132
  • Heo, H. J. , Kim, M. J. , Lee, J. M. , Choi, S. J. , Cho, H. Y. , Hong, B. , Kim, H. K. , Kim, E., Shin, D. H.. (2004). Naringenin from Citrus junos has an inhibitory effect on acetylcholinesterase and a mitigating effect on amnesia. Dementia and Geriatric Cognitive Disorders, 17, 151-157. https://doi.org/10.1159/000076349
  • Katritzky, A. R. & Lagowski, J. M. (1963). Prototropic Tautomerism of Heteroaromatic Compounds: I. General Discussion and Methods of Study. Advances in Heterocyclic Chemistry, 1, 311-338. https://doi.org/10.1016/S0065-2725(08)60528-0
  • Kilic, B., Gulcan, H. O. , Aksakal, F. (2018). Design and synthesis of some new carboxamide and propanamide derivatives bearing phenylpyridazine as a core ring and the investigation of their inhibitory potential on in-vitro acetylcholinesterase and butyrylcholinesterase. Bioorganic Chemistry, 79, 235-249. https://doi.org/10.1016/j.bioorg.2018.05.006
  • Lapinski, L., Nowak, M. J. , Fulara, J. , Les´, A., Adamowicz, L. (1992). Relation between structure and tautomerism in diazinones and diazinethlones. An experimental matrix isolation and theoretical ab initio study. The Journal of Physical Chemistry, 96, 6250–6254.
  • Orhan, S., Aslan, M.İ, Kartal, B.İ Şener, K. H. C. Başer, (2008). Inhibitory effect of Turkish Rosmarinus officinalis L. On acetylcholinesterase and butyrylcholinesterase enzymes. Food Chemistry, 108663-668. https://doi.org/10.1016/j.foodchem.2007.11.023
  • Özçelik, A. B., Özdemir, Z., Sari, S. , Utku, S. , Uysal, M. (2019). A New Series of Pyridazinone Derivatives as Cholinesterases Inhibitors: Synthesis, In Vitro Activity and Molecular Modeling Studies. Pharmacological Reports, 71(6), 1253-1263. https://doi.org/10.1016/j.pharep.2019.07.006
  • Özdemir, Z. , Yılmaz, H., Sarı, S., Karakurt, A., Şenol, F. S., Uysal, M. (2017). Design, synthesis, and molecular modeling of new 3(2H)-pyridazinone derivatives as acetylcholinesterase/butyrylcholinesterase inhibitors. Medicinal Chemistry Research, 26, 2293-2308. https://doi.org/10.1007/s00044-017-1930-x
  • Özdemir, Z., Başak-Türkmen, N., Ayhan, İ., Çiftçi, O.,M. Uysal, M. (2019). Synthesis of New 6-[4-(2-Fluorophenylpiperazine-1-yl)]-3(2H)-pyridazinone-2-acethyl-2-(substitutedbenzal)hydrazone Derivatives and Evulation of Their Cytotoxic Effects in Liver and Colon Cancer Cell Line. Pharmaceutical Chemistry Journal, 52;11, 952-959. https://doi.org/10.1007/s11094-019-01927-y Özdemir, Z.,. Alagöz, M. A. (2019). Anticholinesterases (Eds: I. J. Al-Zwaini, A. AL-Mayahi), Selected Topics in Myasthenia Gravis. 1st edition. London: Intech Open, 69-78. https://doi.org/10.2174/0929867328666210203204710
  • Özten, Ö. , Zengin Kurt, B., Sönmez, F., Doğan, B., Durdagi, S. (2021). Synthesis, molecular docking and molecular dynamics studies of novel tacrine-carbamate derivatives as potent cholinesterase inhibitors. Bioorganic Chemistry, 115105225. https://doi.org/10.1016/j.bioorg.2021.105225
  • Rathish, I. G., Javed, K. , Bano, S., Ahmad, S. ,. Alam, M. S., Pillai, K. K. (2009). Synthesis and blood glucose lowering effect of novel pyridazinone substituted benzenesulfonylurea derivatives. European Journal of Medicinal Chemistry, 44, 2673-2678. https://doi.org/10.1016/j.ejmech.2008.12.013
  • Roth, G. J. , Heckel, A., Kley, J. T. (2015). Design, synthesis and evaluation of MCH receptor 1 antagonists-Part II: optimization of pyridazines toward reduced phospholipidosis and hERG inhibition. Bioorganic & Medicinal Chemistry Letters, 25, 3270-3274. https://doi.org/10.1016/j.bmcl.2015.05.074
  • Sabt, A., Eldehna, W. M. , Al-Warhi, T. ,. Alotaibi, O. J., Elaasser, M. M. , Suliman, H., Abdel-Aziz, H. A. (2020). Discovery of 3,6- disubstituted pyridazines as a novel class of anticancer agents targeting cyclin-dependent kinase 2: synthesis, biological evaluation and in silico insights Journal of Enzyme Inhibition and Medicinal Chemistry, 35(1), 1616-1630. https://doi.org/10.1080/14756366.2020.1806259
  • Sameem, B., Saeedi,M., Mahdavi, M., Shafiee, A. (2018). A review on tacrine-based scaffolds as multi-target drugs (MTDLs) for Alzheimer's disease. European Journal of Medicinal Chemistry, 128(10), 332-345. https://doi.org/10.1016/j.ejmech.2016.10.060
  • Schmidt, P. , Druey, J. (1954). Heilmittelchemische Studien in der heterocyclischen Reihe. 10. Mitteilung. Pyridazine VII. Zur neuen Pyridazin-Synthese.Methylpyridazine. Helvetica Chimica Acta. 37(5), 1467-1471. https://doi.org/10.1002/HLCA.19540370514
  • Tan, O. U. , Ozadali, K. , Yogeeswari, P. (2012). Synthesis and antimycobacterial activities of some new N-acylhydrazone and thiosemicarbazide derivatives of 6-methyl-4,5-dihydropyridazin-3(2H)-one. Medicinal Chemistry Research, 21, 2388-2394. https://doi.org/10.1007/s00044-011-9770-6
  • Türkeş, C., Akocak, S. , Işık, M., Lolak, N., Taslimi, P., Durgun, M., Gülçin, İ. , Budak, Y. , Beydemir, Ş. (2021). Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitors. Journal of Biomolecular Structure and Dynamics, 40(5), 1-13. https://doi.org/10.1080/07391102.2021.1916599
  • Utku, I. , Gökçe, M., Aslan, G., Bayram, G. , Ülger, M., Emekdaş, G., Şahin, M. F. (2011). Synthesis and in vitro antimycobacterial activities of novel 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(substituted/nonsubstituted acetophenone) hydrazine. Arzneimittelforschung, 61(1), 1-7. https://doi.org/10.3906/kim-1009-63
  • Utku, S ., Gökçe, M., Orhan, İ., Şahin, M. F. (2011). Synthesis of novel 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(substituted/-nonsubstituted benzal)hydrazone derivatives and acetylcholinesterase and butyrylcholinesterase inhibitory activities in vitro. Journal of Chemistry, 829(35), 331-339. https://doi.org/10.1055/s-0031-1296161.
  • Yamali, C., Ozan, G. H. , Kahya, B., Çobanoğlu, S., Şüküroğlu, M. K., Doğruer, D. S. (2015). Synthesis of some 3(2H)-pyridazinone and 1(2H)-phthalazinone derivatives incorporating aminothiazole moiety and investigation of their antioxidant, acetylcholinesterase, and butyrylcholinesterase inhibitory activities. Medicinal Chemistry Research, 24, 1210-1217. https://doi.org/10.1007/s00044-014-1205-8
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri
Bölüm Makaleler
Yazarlar

Azime Berna Özçelik 0000-0002-3160-5753

Hasan Erkan Rüzgar Bu kişi benim 0000-0003-1756-8383

Fatma Sezer Şenol Deniz Bu kişi benim 0000-0002-5850-9841

İlkay Erdoğan Orhan 0000-0002-7379-5436

Mehmet Abdullah Alagöz 0000-0001-5190-7196

Zeynep Özdemir 0000-0003-4559-2305

Proje Numarası 02/2017-22
Yayımlanma Tarihi 31 Ağustos 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 4 Sayı: 2

Kaynak Göster

APA Özçelik, A. B., Rüzgar, H. E., Şenol Deniz, F. S., Erdoğan Orhan, İ., vd. (2022). Novel 2,6-disubstituted-3-(2H)-pyridazones as Cholinesterase Inhibitors: In vitro Enzyme Inhibition and In silico Molecular Modelling and Dynamic Studies. Journal of Gazi University Health Sciences Institute, 4(2), 80-95.
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