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腙-磺酸盐杂合体作为潜在的胆碱酯酶抑制剂:设计、合成与分子模拟研究。

Hydrazone-sulfonate hybrids as potential cholinesterase inhibitors: design, synthesis and molecular modeling simulation.

机构信息

Chemistry of Natural & Microbial Products Department, Pharmaceutical & Drug Industries Research Institute, National Research Centre, Dokki, Giza, 12622, Egypt.

Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo, 11562, Egypt.

出版信息

Future Med Chem. 2023 Dec;15(24):2269-2287. doi: 10.4155/fmc-2023-0238. Epub 2023 Nov 23.

Abstract

Design and synthesis of a series of hydrazone-sulfonate hybrids, . The inhibitory properties of the synthesized compounds against acetylcholinesterase and butyrylcholinesterase were evaluated using donepezil as the reference standard. Compound was identified as the most potent inhibitor of acetylcholinesterase (IC = 9.30 μM), and compound was the most potent inhibitor of butyrylcholinesterase (IC = 11.82 μM). To confirm the safety of the most potent hits at the used doses, toxicological bioassays were conducted. Molecular docking was performed and the tested derivatives were found to fit well in the active sites of both enzymes. This study provides valuable insights into the potential of hydrazone-sulfonate hybrids as drug candidates.

摘要

设计并合成了一系列腙-磺酸盐杂合化合物,。采用多奈哌齐作为参考标准,评估了合成化合物对乙酰胆碱酯酶和丁酰胆碱酯酶的抑制特性。化合物被鉴定为乙酰胆碱酯酶的最强抑制剂(IC = 9.30 μM),化合物是丁酰胆碱酯酶的最强抑制剂(IC = 11.82 μM)。为了确认在使用剂量下最有效化合物的安全性,进行了毒理学生物测定。进行了分子对接,发现测试的衍生物与两种酶的活性部位结合良好。这项研究为腙-磺酸盐杂合物作为药物候选物的潜力提供了有价值的见解。

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