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

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.