Teke Tunçel Şenel, Sıcak Yusuf, Özbek M Oluş, Uba Abdullahi Ibrahim, Karaküçük-İyidoğan Ayşegül, Oruç-Emre Emine Elçin
Department of Molecular Biology and Genetics, İstanbul Arel University, Istanbul, Turkey.
Department of Medicinal and Aromatic Plants, Köyceğiz Vocational School, Muğla Sıtkı Koçman University, Muğla, Turkey.
Chirality. 2025 Jul;37(7):e70041. doi: 10.1002/chir.70041.
A new series of chiral hydrazide-hydrazone derivatives were synthesized and evaluated their acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase and urease inhibition and antioxidant activities. The chemical structures of newly synthesized chiral aryl hydrazide-hydrazone derivatives were clarified using UV-Vis, IR, H and C NMR, and mass spectroscopies. According to NMR data, due to the partial double bond character of the amide C-N bond, two conformational isomers (E and Z) exist in solution. Based on this information, the conformational properties of the synthesized compounds were investigated using temperature-dependent NMR spectroscopy and DFT. The results of DFT studies revealed that E-E conformer is the most stable structure for the synthesized hydrazones. In addition, the enzyme inhibition potentials of the synthesized compounds were evaluated. Among all chiral hydrazide-hydrazones, compound 3b (containing nitro group in the hydrazone part) had the best inhibition profile against AChE, whereas compound 3d was found to be the most active compound against BChE. In addition, compound 3d, which carries a methoxy group in both the benzamide and the hydrazone moiety, attracted attention due to its good activity against all examined enzymes. Furthermore, molecular docking calculations were performed to get insights into the interaction patterns between the synthesized compounds and the selected target protein.
合成了一系列新的手性酰肼腙衍生物，并评估了它们对乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BChE）、酪氨酸酶和脲酶的抑制作用以及抗氧化活性。利用紫外可见光谱、红外光谱、氢核磁共振谱、碳核磁共振谱和质谱对新合成的手性芳基酰肼腙衍生物的化学结构进行了表征。根据核磁共振数据，由于酰胺C-N键具有部分双键性质，溶液中存在两种构象异构体（E型和Z型）。基于此信息，使用变温核磁共振光谱和密度泛函理论（DFT）研究了合成化合物的构象性质。DFT研究结果表明，E-E构象异构体是合成腙最稳定的结构。此外，还评估了合成化合物的酶抑制潜力。在所有手性酰肼腙中，化合物3b（腙部分含有硝基）对AChE具有最佳的抑制作用，而化合物3d被发现是对BChE最具活性的化合物。此外，在苯甲酰胺和腙部分均带有甲氧基的化合物3d，因其对所有检测酶都具有良好的活性而受到关注。此外，还进行了分子对接计算，以深入了解合成化合物与选定靶蛋白之间的相互作用模式。
