新型二萜内酯化合物Euphorikanin A的结构和性质计算分析  

Theoretical Study on the Structure and Properties of a Novel Diterpenoid Lactone Compound Euphorikanin A

作　　者：徐佳禛 王长江[1] 王朝杰 XU Jia-zhen;WANG Chang-jiang;WANG Chao-jie(Department of Pharmacy,The Second Affiliated Hospital of Jiaxing University,Jiaxing 314000,China;Department of Pharmacy,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China)

机构地区：[1]嘉兴学院附属第二医院医学部,浙江嘉兴314000 [2]温州医科大学药学院药学系,浙江温州325035

出　　处：《光谱学与光谱分析》2025年第2期371-378,共8页Spectroscopy and Spectral Analysis

基　　金：国家自然科学基金项目(21177098);浙江省自然科学基金项目(LY16B070006)资助。

摘　　要：化合物Euphorikanin A是从甘遂大戟根中分离出的新型二萜内酯化合物,初步生物活性发现其具有肿瘤细胞毒活性,分析药物的结构、光谱性质和成药可能性是了解其生物活性的必要前提,也可为开发新药提供参考。运用密度泛函理论B3LYP/6-311++G(2d,p)和ωB97XD/6-311++G(2d,p)方法,对化合物Euphorikanin A的药效构象、几何和电子结构、红外(IR)、紫外-可见(UV-Vis)、核磁共振(NMR)谱进行计算,并借助概念密度泛函理论进行分子全局反应指数分析,使用药物代谢动力学平台开展成药性和ADME/Tox评估。计算结果显示Euphorikanin A有唯一药效构像,两种方法和不同溶剂环境中化合物几何结构参数值相近,计算值与晶体参数吻合较好。理论红外光谱特征与实验吻合,水环境中计算的IR光谱更接近真实环境,理论计算校正因子为0.94。Euphorikanin A紫外光谱最大吸收峰在193.88~201.75 nm。两种方法得到的核磁数据理论结果与实验吻合度高,R^(2)均大于0.94。Euphorikanin A的六元环的羟基可能为反应活性位点。Euphorikanin A的全局反应参数和药代动力学表现出良好性能,尤其在Caco-2细胞膜通透性、血脑屏障透过率和人肠道吸收性。Euphorikanin A的结构和性质在成药性拥有优势,具有进一步开发的价值。Euphorikanin A,a recently discovered diterpene lactone compound is dated from the roots of Euphorbia reausui,exhibits promising tumor cytotoxic activity.To comprehend its biological effects fully,it is imperative to investigate its structural characteristics,spectral properties,and potential as a therapeutic agent.Consequently,further examination of its structure and properties can serve as a valuable resource for advancing novel pharmaceuticals.The density functional theory B3LYP/6-311++G(2d,p)andωB97XD/6-311++G(2d,p)methods were applied to calculate the pharmacophoric conformation,geometric and electronic structure,infrared(IR),ultraviolet-visible(UV-Vis),nuclear magnetic resonance(NMR)spectra of the compound Euphorikanin A,and the molecular global reaction index analysis was carried out by using conceptual density functional theory.The pharmacokinetics platform was used to evaluate druggability and ADME/Tox.The calculation results showed that Euphorikanin A has a unique pharmacophoric conformation,and the geometric structure parameters of the compound were similar in both methods and different solvent environments.The calculated values were in good agreement with the crystal parameters.The theoretical infrared spectral characteristics are consistent with the experiment,and the calculated infrared spectra in the water environment are closer to the real values,with a theoretical scaling factor of 0.94.The maximum absorption peak of Euphorikanin A in the UV-Vis spectrum is between 193.88 and 201.75 nm.The theoretical results of the nuclear magnetic data obtained by both methods agree well with the experimental results,with R^(2) greater than 0.94.The hydroxyl group of the six-membered ring of Euphorikanin A may be the reaction's active site.The compound's global reaction parameters and pharmacokinetics showed good performance,especially regarding Caco-2 cell membrane permeability,blood-brain barrier permeability,and human intestinal absorption.The structure and properties of Euphorikanin A have advantages in dru

关 键 词：Euphorikanin A 密度泛函理论 电子结构 反应指数 成药性 

分 类 号：O641.3[理学—物理化学]