Department of Chemistry, Faculty of Science, Kahramanmaras Sütcü Imam University, Kahramanmaras, Turkey.
Chem Biol Drug Des. 2023 Oct;102(4):676-691. doi: 10.1111/cbdd.14274. Epub 2023 May 31.
A series of hydrazide-hydrazone imine derivative compounds (3a-k) were synthesized and their structures characterized using FTIR, H, and C (NMR) spectroscopic methods. In addition, molecular structures of compounds 3a, 3d, and 3g were elucidated by X-ray diffraction technique. In vitro inhibition activities of hydrazide-hydrazone imine derivatives against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were investigated. Compound 3i (IC = 2.01 μM) exhibited the best inhibitory activity against AChE, comparable to the control Galantamine (IC = 2.60 μM). Against BChE, compound 3h (IC = 2.83 μM) showed the best inhibitory property which is higher control Galantamine (IC = 3.70 μM). The Ki values of compound 3i (Ki = 0.63 μM) and compound 3h (Ki = 0.94 μM) that have the strongest inhibitory potential were determined against AChE and BChE, respectively. According to the docking result, the most stable conformation of AChE and compound 3i showed that it has a binding affinity of -10.82 kcal/moL. The binding affinity of the most stable conformation formed by BChE and compound 3h is -8.60 kcal/moL. Finally, in silico results and pharmacokinetic parameters of ADME showed that these compounds have good oral bioavailability properties.
一系列酰腙腙亚胺衍生物化合物（3a-k）被合成，并通过傅里叶变换红外光谱（FTIR）、氢（1H）和碳（13C）核磁共振（NMR）光谱方法对其结构进行了表征。此外，化合物 3a、3d 和 3g 的分子结构通过 X 射线衍射技术进行了阐明。体外抑制乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的酰腙腙亚胺衍生物的活性进行了研究。化合物 3i（IC = 2.01 μM）对 AChE 的抑制活性最好，与对照加兰他敏（IC = 2.60 μM）相当。在 BChE 中，化合物 3h（IC = 2.83 μM）显示出最好的抑制活性，高于对照加兰他敏（IC = 3.70 μM）。对 AChE 和 BChE 抑制潜力最强的化合物 3i（Ki 值=0.63 μM）和化合物 3h（Ki 值=0.94 μM）的 Ki 值分别进行了测定。根据对接结果，AChE 最稳定构象和化合物 3i 显示其具有-10.82 kcal/moL 的结合亲和力。BChE 和化合物 3h 形成的最稳定构象的结合亲和力为-8.60 kcal/moL。最后，基于 ADME 的计算结果和药代动力学参数表明，这些化合物具有良好的口服生物利用度特性。
