脒基硫脲、硫代脒基硫脲、噻唑和噁唑类似物作为单胺氧化酶抑制剂的研究：合成、表征、生物评价、分子对接和动力学研究。

Semicarbazones, thiosemicarbazone, thiazole and oxazole analogues as monoamine oxidase inhibitors: Synthesis, characterization, biological evaluation, molecular docking, and kinetic studies.

机构信息

Research Institute of Pharmaceutical Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi 75270, Pakistan.

出版信息

Bioorg Chem. 2021 Oct;115:105209. doi: 10.1016/j.bioorg.2021.105209. Epub 2021 Jul 27.

DOI:10.1016/j.bioorg.2021.105209

PMID:34364054

Abstract

A series of semicarbazone, thiosemicarbazone, thiazole, and oxazole derivatives were designed, synthesized, and examined for monoamine oxidase inhibition using two isoforms, i.e., MAO-A and MAO-B. Among all the analogues, 3c and 3j possessed substantial activity against MAO-A with IC values of 5.619 ± 1.04 µM and 0.5781 ± 0.1674 µM, respectively. Whereas 3d and 3j were active against monoamine oxidase B with the IC values of 9.952 ± 1.831 µM and 3.5 ± 0.7 µM, respectively. Other derivatives active against MAO-B were 3c and 3g with the IC values of 17.67 ± 5.6 µM and 37.18 ± 2.485 µM. Moreover, molecular docking studies were achieved for the most potent compound (3j) contrary to human MAO-A and MAO-B. Kinetic studies were also performed for the most potent analogue to evaluate its mode of interaction with MAO-A and MAO-B.

摘要

一系列的缩氨基脲、硫代缩氨基脲、噻唑和噁唑衍生物被设计、合成并通过两种同型酶，即 MAO-A 和 MAO-B 进行单胺氧化酶抑制活性测试。在所有的类似物中，化合物 3c 和 3j 对 MAO-A 具有显著的抑制活性，IC 值分别为 5.619 ± 1.04 μM 和 0.5781 ± 0.1674 μM。而化合物 3d 和 3j 对单胺氧化酶 B 的抑制活性较好，IC 值分别为 9.952 ± 1.831 μM 和 3.5 ± 0.7 μM。其他对 MAO-B 有活性的衍生物为 3c 和 3g，IC 值分别为 17.67 ± 5.6 μM 和 37.18 ± 2.485 μM。此外，针对最有效的化合物（3j）与人类 MAO-A 和 MAO-B 进行了分子对接研究。还对最有效的类似物进行了动力学研究，以评估其与 MAO-A 和 MAO-B 的相互作用模式。