摘要/Abstract

以天然β-蒎烯衍生物诺蒎酮为原料，经缩合和环化等反应，合成了24个诺蒎酮基噻唑腙类化合物，采用¹H NMR，¹³C NMR，HRMS等方法对其结构进行表征，研究了噻唑腙类化合物对α-淀粉酶的抑制活性.结果表明，与阳性对照阿卡波糖相比，有6种化合物对α-淀粉酶表现出优良的的抑制活性，其中4-（2-（2-（6，6-二甲基-3-（4-甲基苄亚基）双环[3.1.1]庚烷-2-亚基）肼基）噻唑-4-基）苯酚（SZ14）的IC₅₀值可达到4.11 μmol/L.从化合物的结构与活性关系看，R²的结构对活性具有显著的影响.抑制动力学结果表明，这6种化合物是针对α-淀粉酶的非竞争性抑制剂.采用分子对接方法评价了噻唑腙类化合物与α-淀粉酶的结合亲和力，并分析探索了化合物SZ14与α-淀粉酶的结合方式.
关键词: 诺蒎酮, 噻唑腙, α-淀粉酶抑制剂, 分子对接
A series of nopinone-based thiazolyhydrazone derivatives were synthesized by using nopinone derivated from natural β-pinene as the starting material in three steps, including aldol reaction with aromatic aldehydes, condensation with aminothiourea, and cyclization with bromoacetophenone. The structures of synthesized compounds were characterized by ¹H NMR, ¹³C NMR and HRMS. α-Amylase inhibitory activities of these compounds were also investigated. The results showed that 6 compounds among them had good inhibitory activities compared with the positive control acarbose. Especially, 4-(2-(2-(6,6-dimethyl-3-(4-methylbenzylidene))bicyclo[3.1.1]heptane-2-ylidene)indolyl-4-thiazol-4-yl)phenol (SZ14) exhibited remarkable α-amylase inhibitory activity with IC₅₀ value of 4.11 μmol/L. From the structure-activity relationship, the structure of R² gave great influence on the activities of thiazolyhydrazone derivatives. The kinetic inhibition study revealed that those 6 compounds were the noncompetitive inhibitor against α-amylase. It was used for molecular docking study to find out binding affinities for thiazolylhydrazone derivatives, and the binding mode of compound SZ14 with α-amylase was primarily investigated with molecular docking method.
Key words: nopinone, thiazolylhydrazone, α-amylase inhibitor, molecular docking


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