Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, İstanbul, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey; Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu Universty, Eskişehir, Turkey.
Bioorg Chem. 2019 Mar;84:41-50. doi: 10.1016/j.bioorg.2018.11.016. Epub 2018 Nov 17.
In the current work, Schiff base derivatives of antipyrine were synthesized. The chemical characterization of the compounds was confirmed using IR, H NMR, C NMR and mass spectroscopies. The inhibitory potency of synthesized compounds was investigated towards acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidases A and B (MAO-A and MAO-B) enzymes. Some of the compounds displayed significant inhibitory activity against AChE and MAO-B enzymes, respectively. According to AChE enzyme inhibition assay, compounds 3e and 3g were found as the most potent derivatives with IC values of 0.285 µM and 0.057 µM, respectively. Also, compounds 3a (IC = 0.114 µM), 3h (IC = 0.049 µM), and 3i (IC = 0.054 µM) were the most active derivatives against MAO-B enzyme activity. So as to understand inhibition type, enzyme kinetics studies were carried out. Furthermore, molecular docking studies were performed to define and evaluate the interaction mechanism between compounds 3g and 3h and related enzymes. ADME (Absorption, Distribution, Metabolism, and Excretion) and BBB (Blood, Brain, Barier) permeability predictions were applied to estimate pharmacokinetic profiles of synthesized compounds.
在当前的工作中，合成了安替比林的席夫碱衍生物。通过红外光谱（IR）、核磁共振氢谱（H NMR）、核磁共振碳谱（C NMR）和质谱等方法对化合物进行了化学表征。研究了合成化合物对乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BuChE）和单胺氧化酶 A 和 B（MAO-A 和 MAO-B）的抑制活性。一些化合物对 AChE 和 MAO-B 酶表现出显著的抑制活性。根据 AChE 酶抑制测定，化合物 3e 和 3g 被发现是最有效的衍生物，IC 值分别为 0.285µM 和 0.057µM。此外，化合物 3a（IC=0.114µM）、3h（IC=0.049µM）和 3i（IC=0.054µM）对 MAO-B 酶活性的抑制作用最强。为了了解抑制类型，进行了酶动力学研究。此外，还进行了分子对接研究，以确定和评估化合物 3g 和 3h 与相关酶之间的相互作用机制。应用 ADME（吸收、分布、代谢和排泄）和 BBB（血脑屏障）渗透性预测来估计合成化合物的药代动力学特征。
