Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme

ERGÜN, Muhammed; UYSAL, Mehtap; BOZBEY, İrem; TÜRKMENOĞLU, Burçin; DİLEK, Esra; ÖNEL, Gülce TAŞKOR; ÖZÇELİK, Azime Berna; GÜRSOY, Şule

doi:10.29228/jrp.239

Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme

İrem BOZBEY, (Erzincan Binali Yıldırım Üniversitesi Eczacılık Fakültesi Farmasötik Kimya Anabilim Dalı, Erzincan, Türkiye)

Gülce TAŞKOR ÖNEL, (Erzincan Binali Yıldırım Üniversitesi, Eczacılık Fakültesi, Analitik Kimya Anabilim Dalı, Erzincan, Türkiye)

Burçin TÜRKMENOĞLU, (Erzincan Binali Yıldırım Üniversitesi, Eczacılık Fakültesi, Analitik Kimya Anabilim Dalı, Erzincan, Türkiye)

Şule GÜRSOY, (Erzincan Binali Yıldırım Üniversitesi, Eczacılık Fakültesi Biyokimya Anabilim Dalı, Erzincan, Türkiye)

Esra DİLEK, (Erzincan Binali Yıldırım Üniversitesi, Eczacılık Fakültesi Biyokimya Anabilim Dalı, Erzincan, Türkiye)

Muhammed ERGÜN, (Cumhuriyet Üniversitesi, Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı, Sivas, Türkiye)

Azime Berna ÖZÇELİK, (Gazi Üniversitesi, Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı, Ankara, Türkiye)

Mehtap UYSAL (Erzincan Binali Yıldırım Üniversitesi Eczacılık Fakültesi Farmasötik Kimya Anabilim Dalı, Erzincan, Türkiye)

Journal of research in pharmacy (online)

13 0

Yıl: 2022 Cilt: 26 Sayı: 5 Sayfa Aralığı: 1461 - 1471 Metin Dili: İngilizce DOI: 10.29228/jrp.239 İndeks Tarihi: 29-09-2022

Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme

Öz:

Alzheimer's disease is a neurological disease characterized by the destruction of brain cells. In this disease, which causes a decrease in thought, memory and behavioral functions, the symptoms appear gradually with age. In this study, inhibition of acetylcholinesterase enzyme which is an important target in accordance with the cholinergic hypothesis, was studied. New 3(2H)pyridazinone-triazole derivatives were synthesized, confirmed by 1H-NMR, 13CNMR, HRMS analysis and their IC50 and Ki values were studied. The inhibition constants (Ki) of the compounds against the AChE enzyme ranged from 2.35 ± 0.18 to 5.15 ± 0.46 μM. The compound with the best inhibitory properties was compound 6d with a Ki value of 2.35 ± 0.18 μM. In addition, to support the experimental data, molecular docking studies were carried out with 6b, 6d, 6e and 6f compounds with AChE crystal structure (PDB ID:4M0E).

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

[1] Ulep-Reed M, Saraon S, McLea S. Alzheimer Disease. The Journal for Nurse Practitioners. 2017;14. [CrossRef]
[2] Zhang P, Xu S, Zhu Z, Xu J. Multi-target design strategies for the improved treatment of Alzheimer's disease. Eur J Med Chem. 2019;176:228-47. [CrossRef]
[3] Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet. 1976;2(8000):1403. [CrossRef]
[4] Augustinsson KB, Nachmansohn D. Distinction between Acetylcholine-Esterase and Other Choline Estersplitting Enzymes. Science. 1949;110(2847):98-9. [CrossRef]
[5] Kumar A, Singh A, Ekavali. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep. 2015;67(2):195-203. [CrossRef]
[6] Hung S-Y, Fu W-M. Drug candidates in clinical trials for Alzheimer's disease. J Biomed Sci. 2017;24(1):47-. [CrossRef]
[7] Özdemir Z, Alagöz MA, Uslu H, Karakurt A, Erikci A, Ucar G, et al. Synthesis, molecular modelling and biological activity of some pyridazinone derivatives as selective human monoamine oxidase-B inhibitors. Pharmacological Reports. 2020;72(3):692-704. [CrossRef]
[8] Bozbey İ, Özdemir Z, Uslu H, Özçelik AB, Şenol FS, Orhan İ E, et al. A Series of New Hydrazone Derivatives: Synthesis, Molecular Docking and Anticholinesterase Activity Studies. Mini Rev Med Chem. 2020;20(11):1042-60. [CrossRef]
[9] Dubey S, Bhosle PA. Pyridazinone: an important element of pharmacophore possessing broad spectrum of activity. Medicinal Chemistry Research. 2015;24(10):3579-98. [CrossRef]
[10] Antoni Krasin´ski, Zoran Radic´, Roman Manetsch, Jessica Raushel, Palmer Taylor, et al. In Situ Selection of Lead Compounds by Click Chemistry: Target-Guided Optimization of Acetylcholinesterase Inhibitors. J. Am. Chem. Soc. 2005;127:6686-6692. [CrossRef]
[11] Samanesadat Hosseini, Seied Ali Pourmousavi, Mohammad Mahdavi, Parham Taslimi. Synthesis, and in vitro biological evaluations of novel naphthoquinone conjugated to aryl triazole acetamide derivatives as potential anti- Alzheimer agents. J. Mol. Struct. 2022;1255:132229. [CrossRef]
[12] Mina Saeedi, Atefeh Maleki, Aida Iraji, Roshanak Hariri, Tahmineh Akbarzadeh et al. Synthesis and bioevaluation of new multifunctional methylindolinone-1,2,3-triazole hybrids as anti-Alzheimer’s agents. J. Mol. Struct. 2021;1229:129828. [CrossRef]
[13] Mina Saeedi, Maliheh Safavi, Elahe Karimpour-Razkenari, Mohammad Mahdavi, Najmeh Edraki, et al. Synthesis of novel chromenones linked to 1,2,3-triazole ring system:Investigation of biological activities against Alzheimer’s disease. Bioorganic Chemistry. 2017;70:86–93. [CrossRef]
[14] Man Xu, Yongzhi Peng, Li Zhu, Shulin Wang, Jiayou Ji, K.P. Rakesh. Triazole derivatives as inhibitors of Alzheimer's disease: Current developments and structure-activity relationships. Eur. J. Med. Chem. 2019;180:656-672. [CrossRef]
[15] Musa Özil, Halis Türker Balaydın, Murat Şentürk. Synthesis of 5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-one’s aryl Schiff base derivatives and investigation of carbonic anhydrase and cholinesterase (AChE, BuChE) inhibitory properties. Bioorganic Chemistry. 2019;86:705–713. [CrossRef]
[16] Mahnaz Yazdani, Najmeh Edraki, Rashid Badri, Mehdi Khoshneviszadeh, Aida Iraji, Omidreza Firuzi. 5,6 Diphenyl triazine thio methyl triazole hybrid as a new Alzheimer’s disease modifying agents. Molecular Diversity, 2020;24:641–654. [CrossRef]
[17] Ömer Faruk Çöl, İrem Bozbey, Burçin Türkmenoğlu, Mehtap Uysal. 3(2H)-pyridazinone derivatives: Synthesis, in-silico studies, structure-activity relationship and in-vitro evaluation for acetylcholinesterase enzyme inhibition. J. Mol. Struct. 2022;1261:132970
[18] Çeçen M, Oh JM, Özdemir Z, Büyüktuncel SE, Uysal M, Abdelgawad MA, et al. Design, Synthesis, and Biological Evaluation of Pyridazinones Containing the (2-Fluorophenyl) Piperazine Moiety as Selective MAO-B Inhibitors. Molecules. 2020;25(22). [CrossRef]
[19] Wujec M, Pachuta-Stec A, Stefańska J, Kuśmierz E, Siwek A. Synthesis and Antibacterial Activity of Some New Derivatives of Thiosemicarbazide and 1,2,4-Triazole. Phosphorus, Sulfur, and Silicon and the Related Elements. 2013;188(11):1661-9.[CrossRef]
[20] Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology. 1961;7(2):88-95. [CrossRef]
[21] Shirinzadeh H, Dilek E, Alım Z. Evaluation of Naphthalenylmethylen Hydrazine Derivatives as Potent Inhibitors on, Antiatherogenic Enzymes, Paraoxonase I and Acetylcholinesterase Activities. ChemistrySelect. 2022;7(5):e202104489. [CrossRef]
[22] Schrödinger Release 2021-2: Glide S, LLC, New York, NY, 2021.
[23] Anil DA, Aydin BO, Demir Y, Turkmenoglu B. Design, synthesis, biological evaluation and molecular docking studies of novel 1H-1, 2, 3-Triazole derivatives as potent inhibitors of carbonic anhydrase, acetylcholinesterase and aldose reductase. J Mol Struct. 2022;1257:132613 [CrossRef]
[24] Schrödinger Release 2021-2: LigPrep S, LLC, New York, NY, 2021.
[25] Cheung J, Gary EN, Shiomi K, Rosenberry TL. Structures of Human Acetylcholinesterase Bound to Dihydrotanshinone I and Territrem B Show Peripheral Site Flexibility. Acs Medicinal Chemistry Letters. 2013;4(11):1091- 6. [CrossRef]
[26] Schrödinger Release 2021-2: Protein Preparation Wizard; Epik S, LLC, New York, NY, 2021; Impact, Schrödinger, LLC, New York, NY; Prime, Schrödinger, LLC, New York, NY, 2021.

APA	BOZBEY İ, ÖNEL G, TÜRKMENOĞLU B, GÜRSOY Ş, DİLEK E, ERGÜN M, ÖZÇELİK A, UYSAL M (2022). Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme. , 1461 - 1471. 10.29228/jrp.239
Chicago	BOZBEY İrem,ÖNEL Gülce TAŞKOR,TÜRKMENOĞLU Burçin,GÜRSOY Şule,DİLEK Esra,ERGÜN Muhammed,ÖZÇELİK Azime Berna,UYSAL Mehtap Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme. (2022): 1461 - 1471. 10.29228/jrp.239
MLA	BOZBEY İrem,ÖNEL Gülce TAŞKOR,TÜRKMENOĞLU Burçin,GÜRSOY Şule,DİLEK Esra,ERGÜN Muhammed,ÖZÇELİK Azime Berna,UYSAL Mehtap Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme. , 2022, ss.1461 - 1471. 10.29228/jrp.239
AMA	BOZBEY İ,ÖNEL G,TÜRKMENOĞLU B,GÜRSOY Ş,DİLEK E,ERGÜN M,ÖZÇELİK A,UYSAL M Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme. . 2022; 1461 - 1471. 10.29228/jrp.239
Vancouver	BOZBEY İ,ÖNEL G,TÜRKMENOĞLU B,GÜRSOY Ş,DİLEK E,ERGÜN M,ÖZÇELİK A,UYSAL M Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme. . 2022; 1461 - 1471. 10.29228/jrp.239
IEEE	BOZBEY İ,ÖNEL G,TÜRKMENOĞLU B,GÜRSOY Ş,DİLEK E,ERGÜN M,ÖZÇELİK A,UYSAL M "Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme." , ss.1461 - 1471, 2022. 10.29228/jrp.239
ISNAD	BOZBEY, İrem vd. "Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme". (2022), 1461-1471. https://doi.org/10.29228/jrp.239

APA	BOZBEY İ, ÖNEL G, TÜRKMENOĞLU B, GÜRSOY Ş, DİLEK E, ERGÜN M, ÖZÇELİK A, UYSAL M (2022). Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme. Journal of research in pharmacy (online), 26(5), 1461 - 1471. 10.29228/jrp.239
Chicago	BOZBEY İrem,ÖNEL Gülce TAŞKOR,TÜRKMENOĞLU Burçin,GÜRSOY Şule,DİLEK Esra,ERGÜN Muhammed,ÖZÇELİK Azime Berna,UYSAL Mehtap Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme. Journal of research in pharmacy (online) 26, no.5 (2022): 1461 - 1471. 10.29228/jrp.239
MLA	BOZBEY İrem,ÖNEL Gülce TAŞKOR,TÜRKMENOĞLU Burçin,GÜRSOY Şule,DİLEK Esra,ERGÜN Muhammed,ÖZÇELİK Azime Berna,UYSAL Mehtap Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme. Journal of research in pharmacy (online), vol.26, no.5, 2022, ss.1461 - 1471. 10.29228/jrp.239
AMA	BOZBEY İ,ÖNEL G,TÜRKMENOĞLU B,GÜRSOY Ş,DİLEK E,ERGÜN M,ÖZÇELİK A,UYSAL M Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme. Journal of research in pharmacy (online). 2022; 26(5): 1461 - 1471. 10.29228/jrp.239
Vancouver	BOZBEY İ,ÖNEL G,TÜRKMENOĞLU B,GÜRSOY Ş,DİLEK E,ERGÜN M,ÖZÇELİK A,UYSAL M Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme. Journal of research in pharmacy (online). 2022; 26(5): 1461 - 1471. 10.29228/jrp.239
IEEE	BOZBEY İ,ÖNEL G,TÜRKMENOĞLU B,GÜRSOY Ş,DİLEK E,ERGÜN M,ÖZÇELİK A,UYSAL M "Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme." Journal of research in pharmacy (online), 26, ss.1461 - 1471, 2022. 10.29228/jrp.239
ISNAD	BOZBEY, İrem vd. "Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme". Journal of research in pharmacy (online) 26/5 (2022), 1461-1471. https://doi.org/10.29228/jrp.239