穿心莲内酯衍生物的合成及其体外肾毒性筛选  

Synthesis and in vitro Nephrotoxicity Evaluation of Andrographolide Derivatives

作　　者：余青青 谷丽丽 黄文海[2] 陆红[1] 张信岳[2] YU Qingqing;GU Lili;HUANG Wenhai;LU Hong;ZHANG Xinyue(School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou 311402;Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013)

机构地区：[1]浙江中医药大学药学院,浙江杭州311402 [2]浙江省医学科学院药物研究所,浙江杭州310013

出　　处：《中国医药工业杂志》2019年第3期296-301,共6页Chinese Journal of Pharmaceuticals

基　　金：浙江省自然科学基金项目(LY18H280013)

摘　　要：以天然产物穿心莲内酯为原料,对其C3、C14和C19-位羟基进行修饰,合成了6个穿心莲内酯14-位羟基酯化衍生物,6个脱除C14-位羟基的脱水穿心莲内酯衍生物,以及5个C14-位脱水、C3-位氧化的穿心莲内酯衍生物。这17个目标化合物的结构均经核磁和质谱确证。采用MTT法,选用人肾小管上皮细胞(HK-2)进行初步体外肾毒性研究。结果显示,C14-位羟基酯化衍生物对HK-2细胞的毒性作用高于穿心莲内酯,而脱除C14-位羟基的脱水穿心莲内酯衍生物的毒性作用显著低于穿心莲内酯。In this study, C3, C14 and C19-hydroxyl groups of andrographolide were modified. Six C14-esterified andrographolide derivatives, six C14-dehydrated andrographolide derivatives, and five C14-dehydrated and C3-oxidized andrographolide derivatives were synthesized. The structures of these seventeen target compounds were confirmed by NMR and MS. The in vitro nephrotoxicity against human normal renal tubular epithelial cell (HK-2) were evaluated by MTT assay. The results showed that, the toxicity of C14-esterified derivatives to HK-2 cell was higher than that of andrographolide, while the toxicity of dehydrated andrographolide derivatives which removed C14-hydroxyl group was significantly lower than that of andrographolide.

关 键 词：穿心莲内酯 衍生物 人肾小管上皮细胞 肾毒性 

分 类 号：R914.5[医药卫生—药物化学]