Zhao Zefeng, Lei Mengchen, Wang Yongqi, Bai Yujun, Qiao Haifa
Institute for Chinese Medicine Frontier Interdisciplinary Science and Technology, Shaanxi University of Chinese Medicine, Xianyang 712046, China.
Biomedicine Key Laboratory of Shaanxi Province, Northwest University, 229 Taibai Road, Xi'an 710069, China.
Pharmaceuticals (Basel). 2025 Sep 1;18(9):1312. doi: 10.3390/ph18091312.
: Epilepsy is a cluster of central nervous system (CNS) disorders identified by recurrent seizures, which affects about 60 million people around the world. In this research, a total of 40 types of 3,4,5-trimethoxycinnamic acid (TMCA) piperazine amide derivatives were designed and synthesized, inspired by the traditional Chinese medicine (TCM) herb pair drugs and , followed by determination of their anticonvulsant potency. : All the TMCA analogues were tested for their anticonvulsant potential through two acute models of seizures induced in mice: the maximal electroshock (MES) and sc-pentylenetetrazole (PTZ) models. In addition, the lactate dehydrogenase (LDH) inhibitory activity was determined in vitro. : The results showed that compounds , , , , , and exhibited preferable anticonvulsant activity in the primary evaluation. In addition, the molecular docking results predicted good interactions of screened analogues with the LDH. Molecular dynamic simulation was used to reveal the consensual binding affinity between the most promising compound () and active site interactions with LDH. Electroencephalogram (EEG) analysis and silver and immunofluorescence staining were performed to illustrate the anti-epilepsy potential of compound . : Novel derivatives in this study provide new cores for the further design and optimization inspired by TCM herb pair drugs and , with the aim to explore new anticonvulsant agents.
癫痫是一组以反复发作性癫痫发作为特征的中枢神经系统（CNS）疾病，全球约有6000万人受其影响。在本研究中，受中药药对 和 的启发，设计并合成了总共40种3,4,5-三甲氧基肉桂酸（TMCA）哌嗪酰胺衍生物，随后测定了它们的抗惊厥效力。：通过在小鼠中诱导的两种急性癫痫发作模型，即最大电休克（MES）和皮下注射戊四氮（PTZ）模型，对所有TMCA类似物的抗惊厥潜力进行了测试。此外，还在体外测定了乳酸脱氢酶（LDH）抑制活性。：结果表明，化合物 、 、 、 、 和 在初步评估中表现出较好的抗惊厥活性。此外，分子对接结果预测了筛选出的类似物与LDH之间有良好的相互作用。利用分子动力学模拟揭示了最有前景的化合物（ ）与LDH活性位点相互作用之间的共识结合亲和力。进行了脑电图（EEG）分析以及银染和免疫荧光染色，以阐明化合物 的抗癫痫潜力。：本研究中的新型衍生物为受中药药对 和 启发的进一步设计和优化提供了新的核心，旨在探索新的抗惊厥药物。
