作为乙酰胆碱酯酶和丁酰胆碱酯酶有效抑制剂的新型双噻唑烷酮类查尔酮类似物的合成和分子对接,Chemistry & Biodiversity

当前位置： X-MOL 学术 › Chem. Biodivers. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

作为乙酰胆碱酯酶和丁酰胆碱酯酶有效抑制剂的新型双噻唑烷酮类查尔酮类似物的合成和分子对接
Chemistry & Biodiversity ( IF 2.3 ) Pub Date : 2022-08-23 , DOI: 10.1002/cbdv.202200323
Rafaqat Hussain ₁ , Fazal Rahim ₁ , Wajid Rehman ₁ , Muhammad Taha ₂ , Shoaib Khan ₁ , Khalid Zaman ₁ , Syed Adnan Ali Shah ₃ , Abdul Wadood ₄ , Syahrul Imran ₅ , Magda H Abdellatif ₆

Affiliation

这项工作报告了从容易获得的氨基硫脲盐酸盐、硫氰酸铵和苯甲醛合成基于双噻唑烷酮的查尔酮类似物 ( 1-20 )的便捷策略。所有新提供的基于双噻唑烷酮的查尔酮类似物 ( 1 – 20 ) 都在体外进行了乙酰胆碱酯酶和丁酰胆碱酯酶抑制谱的筛选。值得注意的是，所有合成类似物（除了发现无活性的类似物10、12和 1 4外）在筛选具有IC _{50抑制范围的乙酰胆碱酯酶时显示出中等至良好的抑制潜力}值从 0.070±0.050 到 7.60±0.10 μM，与标准多奈哌齐抑制剂相比，丁酰胆碱酯酶的 IC ₅₀值范围分别为 0.10±0.050 μM 到 10.70±0.20 μM（IC ₅₀ =2.16±0.12 μM），（IC ₅₀ =4.5±0.11 μM)。在该系列中，具有羟基的类似物对乙酰胆碱酯酶和丁酰胆碱酯酶具有优异的抑制潜力。因此，类似物20 (IC ₅₀ =0.070±0.050 μM)、(IC ₅₀ =0.10±0.050 μM)在环A和B的邻位、间位和对位上具有三羟基取代被发现是目前合成系列中最活跃的乙酰胆碱酯酶和丁酰胆碱酯酶抑制剂（1-23 ）。类似物19 (IC ₅₀ =0.15±0.050 μM)、(IC _{50 =0.20±0.050 μM) 在}A环和B环的邻位和间位具有二羟基取代，被确定为对这两种酶的第二强抑制剂. 有趣的是，化合物 ( 16 ) (IC ₅₀=1.50±0.10 μM 针对 AChE）对 AChE 的选择性指数（2.60）优于对 BuChE 的标准多奈哌齐药物（2.083）。不同类型的光谱技术，如 HR-EI-MS、¹ H- 和¹³ C- NMR 用于确认所有新合成类似物的结构。为了找到构效关系，进行了分子对接研究以了解活性抑制剂与酶活性位点的结合方式，结果支持了实验数据。

"点击查看英文标题和摘要"

Synthesis and Molecular Docking of New Bis-Thiazolidinone-Based Chalcone Analogs as Effective Inhibitors of Acetylcholinesterase and Butyrylcholinesterase

This work reports the convenient strategy for the synthesis of bis-thiazolidinone based chalcone analogs (1–20) from readily available thiosemicarbazide hydrochloride, ammonium thiocyanate and benzaldehyde. All the newly afforded bis-thiazolidinone based chalcone analogs (1–20) were screened in vitro for their acetylcholinesterase and butyrylcholinesterase inhibition profile. It was noteworthy, that all the synthetic analogs (except analogs 10, 12 and 14, which are found to be inactive) showed moderate to good inhibitory potentials on screening against acetylcholinesterase having range of inhibitory with IC₅₀ values from 0.070±0.050 to 7.60±0.10 μM, and similarly for butyrylcholinesterase with range IC₅₀ values from 0.10±0.050 μM to 10.70±0.20 μM, respectively as compared to standard Donepezil inhibitor (IC₅₀=2.16±0.12 μM), (IC₅₀=4.5±0.11 μM).Among the series, the analogs with hydroxy group showed superior inhibitory potentials against acetylcholinesterase and butyrylcholinesterase enzymes. Therefore, analog 20 (IC₅₀=0.070±0.050 μM), (IC₅₀=0.10±0.050 μM) bearing trihydroxy substitutions on ortho-, meta- and para-position of both rings A and B was found to be the most active inhibitor of acetylcholinesterase and butyrylcholinesterase enzymes among the current synthesized series (1–23). Analog 19 (IC₅₀=0.15±0.050 μM), (IC₅₀=0.20±0.050 μM) bearing dihydroxy substitutions on ortho- and meta-position of both ring A and ring B was identified as the second most potent inhibitor against both these enzymes. Interestingly, the compound (16) (IC₅₀=1.50±0.10 μM against AChE) has a better selectivity index (2.60) than standard Donepezil drug (2.083) for AChE over BuChE. The different types of spectroscopic techniques such as HR-EI-MS, ¹H- and ¹³C- NMR were used to confirm the structure of all the newly synthetics analogs. To find structure-activity relationship, molecular docking studies were carried out to understand the binding mode of active inhibitors with active site of enzymes and results supported the experimental data.

更新日期：2022-08-23

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>