Laboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Zografou Campus, 15780, Athens, Greece.
Institute of Chemical Biology, National Hellenic Research Foundation, 48, Vas. Constantinou Avenue, 11635, Athens, Greece.
Mol Divers. 2021 May;25(2):723-740. doi: 10.1007/s11030-020-10045-x. Epub 2020 Feb 17.
The present project deals with the investigation of structure-activity relationship of several quinolinone-chalcone and quinolinone-pyrazoline hybrids, in an effort to discover promising antioxidant and anti-inflammatory agents. In order to accomplish this goal, four bioactive hybrid quinolinone-chalcone compounds (8a-8d) were synthesized via an aldol condensation reaction, which were then chemically modified, forming fifteen new pyrazoline analogues (9a-9o). All the synthesized analogues were in vitro evaluated in terms of their antioxidant and soybean lipoxygenase (LOX) inhibitory activity. Among all the pyrazoline derivatives, compounds 9b and 9m were found to possess the best combined activity, whereas 9b analogue exhibited the most potent LOX inhibitory activity, with IC value 10 μM. The in silico docking results revealed that the synthetic pyrazoline analogue 9b showed high AutoDock Vina score (- 10.3 kcal/mol), while all the tested derivatives presented allosteric interactions with the enzyme.
本项目研究了几种喹啉酮-查尔酮和喹啉酮-吡唑啉类化合物的结构-活性关系，旨在发现有前途的抗氧化和抗炎剂。为了实现这一目标，通过醛缩合反应合成了四种具有生物活性的混合喹啉酮-查尔酮化合物（8a-8d），然后对其进行化学修饰，形成了十五种新的吡唑啉类似物（9a-9o）。所有合成的类似物均通过体外抗氧化和大豆脂氧合酶（LOX）抑制活性进行了评估。在所有吡唑啉衍生物中，化合物 9b 和 9m 被发现具有最佳的组合活性，而 9b 类似物表现出最强的 LOX 抑制活性，IC 值为 10 μM。基于分子对接的结果显示，合成的吡唑啉类似物 9b 显示出高 AutoDock Vina 评分（-10.3 kcal/mol），而所有测试的衍生物均与酶呈现出别构相互作用。
