Department of Chemistry, Faculty of Sciences and Arts, Kahramanmaras Sutcu Imam University, TR, 46100, Kahramanmaras, Turkey.
Department of Chemistry, Faculty of Sciences, Ataturk University, 25240-Erzurum, Turkey.
Chem Biodivers. 2022 May;19(5):e202100787. doi: 10.1002/cbdv.202100787. Epub 2022 Apr 5.
In this study, a series of new hybrid molecules containing two important functional groups on the same skeleton were designed. 4-Hydroxybenzaldehyde and its two different derivatives were converted into their respective sulphonates by interacting with tosylchloride and methanesulfonyl chloride. Then, the desired molecules were synthesized by adding diethoxyphosphonate to the aldehyde group. Also, novel synthesis of hybrid compounds (4a-c and 5a-c) were tested toward some metabolic enzymes like carbonic anhydrase I and II isoenzymes (hCA I and hCA II) and acetylcholinesterase (AChE) enzyme. The synthesis of hybrid compounds (4a-c and 5a-c) showed K values of in range of 25.084±4.73-69.853±15.19 nM against hCA I, 32.325±1.67-82.761±22.73 nM against hCA II and 1.699±0.25 and 3.500±0.91 nM against AChE. For these compounds, compound 4c showed maximum inhibition effect against hCA I and hCA II isoenzymes and compound 5b showed maximum inhibition effect against AChE enzyme. By performing docking studies of the most active compounds for their binding modes and interactions were determined.
在这项研究中，设计了一系列在同一骨架上含有两个重要官能团的新型杂化分子。4-羟基苯甲醛及其两种不同的衍生物通过与对甲苯磺酰氯和甲烷磺酰氯相互作用转化为各自的磺酸盐。然后，通过将二乙氧基膦酸酯添加到醛基中合成所需的分子。此外，还对新型杂合化合物（4a-c 和 5a-c）对碳酸酐酶 I 和 II 同工酶（hCA I 和 hCA II）和乙酰胆碱酯酶（AChE）等一些代谢酶的抑制活性进行了测试。杂合化合物（4a-c 和 5a-c）的合成显示，它们对 hCA I 的 K 值在 25.084±4.73-69.853±15.19 nM 范围内，对 hCA II 的 K 值在 32.325±1.67-82.761±22.73 nM 范围内，对 AChE 的 K 值分别为 1.699±0.25 和 3.500±0.91 nM。对于这些化合物，化合物 4c 对 hCA I 和 hCA II 同工酶表现出最大的抑制作用，化合物 5b 对 AChE 酶表现出最大的抑制作用。通过进行对接研究，确定了最活跃化合物的结合模式和相互作用。
J Enzyme Inhib Med Chem. 2014-6-25
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