Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Istanbul, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey; Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
Bioorg Chem. 2021 Jul;112:104917. doi: 10.1016/j.bioorg.2021.104917. Epub 2021 Apr 16.
Thirty novel 2,5-disubstituted-1,3,4-oxadiazole derivatives bearing urea moiety were designed and synthesized. IR, H-NMR, C-NMR and mass spectroscopic methods and elemental analysis were used to confirm the structures of the compounds. Their monoamine oxidase inhibitory activity was determined against the MAO-A and MAO-B isoforms. None of the compounds showed the potent MAO-A inhibitory activity, while the MAO-B inhibition was significantly found in the range of 62 to 98%. Among them, the compounds H8, H9 and H12 bearing chloro substituent at the fourth position of phenylurea were found to show potent monoamine oxidase B inhibitory activity with IC values 0.039-0.066 µM. To define and evaluate the interaction mechanism between compound H8 and monoamine oxidase B, molecular docking studies have been made.
设计并合成了 30 种新型含脲基的 2,5-二取代-1,3,4-噁二唑衍生物。采用红外光谱、核磁共振氢谱、碳谱和质谱以及元素分析等方法对化合物的结构进行了确认。测试了它们对单胺氧化酶-A 和单胺氧化酶-B 同工酶的抑制活性。这些化合物均没有表现出对单胺氧化酶-A 的强烈抑制活性，而对单胺氧化酶-B 的抑制活性范围在 62-98%之间。其中，苯脲的第四位带有氯取代基的化合物 H8、H9 和 H12 被发现对单胺氧化酶 B 具有较强的抑制活性，IC 值为 0.039-0.066µM。为了定义和评估化合物 H8 与单胺氧化酶 B 之间的相互作用机制，进行了分子对接研究。
