新型硫代缩氨基脲席夫碱类单胺氧化酶抑制化合物的合成与生物评价。

Synthesis and Biological Evaluation of New Thiosemicarbazone Derivative Schiff Bases as Monoamine Oxidase Inhibitory Agents.

机构信息

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.

Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.

出版信息

Molecules. 2017 Dec 28;23(1):60. doi: 10.3390/molecules23010060.

DOI:10.3390/molecules23010060

PMID:29283399

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6017703/

Abstract

Twenty-six novel thiosemicarbazone derivative - were synthesized via condensation reactions between the corresponding thiosemicarbazides and aldehydes. The chemical characterization of the compounds was carried out by infrared (IR), mass (MS), proton and carbon nuclear magnetic resonance (¹H- and C-NMR) spectroscopic analyses. The compounds were investigated for their monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) inhibitory activity and most of them were more potent against MAO-A enzyme when compared with MAO-B enzyme. -Cyclohexyl-2-[4-[(4-chlorophenyl)thio]benzylidene]hydrazine-1-carbothioamide () was the most active compound against MAO-A. The enzyme kinetics study revealed that compound has a reversible and competitive mode of binding. Interaction modes between compound and MAO-A were clarified by docking studies. In addition, the favourable absorption, distribution, metabolism, and excretion (ADME) properties and non-toxic nature of compound make this compound a promising MAO-A inhibitor.

摘要

二十六种新型缩硫代氨基脲衍生物 - 通过相应的缩硫代氨基脲与醛之间的缩合反应合成。通过红外（IR）、质谱（MS）、质子和碳核磁共振（¹H- 和 C-NMR）光谱分析对化合物进行了化学表征。研究了这些化合物对单胺氧化酶 A（MAO-A）和单胺氧化酶 B（MAO-B）的抑制活性，与 MAO-B 酶相比，大多数化合物对 MAO-A 酶的抑制活性更强。 -环己基-2-[4-[(4-氯苯基)硫代]苄叉基]肼-1-碳硫酰胺（）对 MAO-A 的抑制活性最高。酶动力学研究表明，化合物以可逆和竞争的结合模式结合。通过对接研究阐明了化合物与 MAO-A 之间的相互作用模式。此外，化合物具有良好的吸收、分布、代谢和排泄（ADME）特性和非毒性，使其成为一种有前途的 MAO-A 抑制剂。