Catalpol has gained increasing attention for its potential contributions in controlling glycolipid metabolism and diabetic complications, which makes used as a very promising scaffold for seeking new anti-diabetic drug candidates. Acylation derivatives of catalpol crotonate (CCs) were designed as drug ligands of glutathione peroxidase (GSH-Px) based on molecular docking (MD) using Surfex-Docking method. Catalpol hexacrotonate (CC-6) was synthesized using microwave assisted method and characterized by FT-IR, NMR, HPLC and HRMS. The MD results indicate that with the increasing of esterification degree of hydroxyl, the C log P of CCs increased significantly, and the calculated total scores (Total_score) of CCs are all higher than that of catalpol. It shows that CCs maybe served as potential lead compounds for neuroprotective agents. It was found that the maximum Total_score of isomers in one group CCs is often not that the molecule with minimum energy. MD calculations show that there are five hydrogen bonds formed between CC-6 and the surrounding amino acid residues. Molecular dynamics simulation results show that the binding of CC-6 with GSH-Px is stable. CC-6 was screened for SH-SY5Y cells viability by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay, the result indicates CC-6 can effectively reverse SZT induced cells apoptosis with dose-dependent manner, which can indirectly show that CC-6 is a potential neuroprotective agent.

Catalpol因其在控制糖脂代谢和糖尿病并发症方面的潜在作用而受到越来越多的关注，这使其成为寻找新的抗糖尿病药物的极有希望的支架。使用Surfex-Docking方法，基于分子对接（MD），将梓醇巴豆酸酯（CCs）的酰化衍生物设计为谷胱甘肽过氧化物酶（GSH-Px）的药物配体。使用微波辅助方法合成了六丁烯醛缩水杨酸酯（CC-6），并通过FT-IR，NMR，HPLC和HRMS对其进行了表征。MD结果表明，随着羟基酯化度的增加，C log PCC的得分显着增加，并且CC的计算总得分（Total_score）均高于catalpol。它表明CCs可能作为神经保护剂的潜在先导化合物。已发现一组CC中异构体的最大Total_score通常不是具有最小能量的分子。MD计算表明，CC-6与周围氨基酸残基之间形成五个氢键。分子动力学模拟结果表明，CC-6与GSH-Px的结合是稳定的。通过MTT（3-（4，5-二甲基噻唑基-2）-2，5-二苯基四唑鎓溴化物）试验筛选CC-6对SH-SY5Y细胞的活力，结果表明CC-6可以有效地逆转SZT诱导的细胞凋亡。依赖方式，可以间接表明CC-6是潜在的神经保护剂。