Kaya Betül, Çevik Ulviye Acar, Çiftçi Bilge, Necip Adem, Işik Mesut, Ay Ebru Nur, Yur Süleyman, Özkay Yusuf, Beydemir Şükrü, Kaplancıklı Zafer Asım
Vocational School of Health Services, Pharmacy Services, Bilecik Şeyh Edebali University, 11230 Bilecik, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
ACS Omega. 2025 Aug 22;10(34):38427-38439. doi: 10.1021/acsomega.5c01055. eCollection 2025 Sep 2.
Ten novel pyrazoline-thiazole derivatives were synthesized and assessed for their potential as acetylcholinesterase and butyrylcholinesterase inhibitors. The structure of the target compounds was characterized by H NMR and C NMR, and purity was determined using HPLC. The in vitro enzyme inhibitory activity assays determined that compounds (IC = 0.382 μM) and (IC = 0.338 μM) showed good inhibitory activity of acetylcholinesterase (AChE). Compound has a selective inhibitory effect on AChE, while compound has a dual effect, being effective against both AChE and BChE (IC = 2.087 μM). The molecular docking results of compound with high inhibitory activity for AChE experimentally showed that it has a strong inhibitory effect close to that of the reference inhibitor tacrine. The compound was found to have the highest activity in its interaction with the BChE (4BDS) protein with a low docking score (-5.555 kcal/mol). Furthermore, the prediction of ADME properties of compounds and was determined through Swiss ADME.
合成了十种新型吡唑啉 - 噻唑衍生物，并评估了它们作为乙酰胆碱酯酶和丁酰胆碱酯酶抑制剂的潜力。通过氢核磁共振（¹H NMR）和碳核磁共振（¹³C NMR）对目标化合物的结构进行了表征，并使用高效液相色谱法（HPLC）测定了纯度。体外酶抑制活性测定表明，化合物（IC₅₀ = 0.382 μM）和（IC₅₀ = 0.338 μM）对乙酰胆碱酯酶（AChE）表现出良好的抑制活性。化合物对AChE具有选择性抑制作用，而化合物具有双重作用，对AChE和丁酰胆碱酯酶（BChE，IC₅₀ = 2.087 μM）均有效。对AChE具有高抑制活性的化合物的分子对接结果实验表明，其具有与参考抑制剂他克林相近的强抑制作用。发现化合物在与BChE（4BDS）蛋白相互作用时活性最高，对接分数较低（-5.555 kcal/mol）。此外，通过瑞士ADME预测了化合物和的药物代谢动力学（ADME）性质。
