穿心莲内酯改构化合物J6的制备及抗肿瘤作用研究
作者:
作者单位:

中国中医科学院广安门医院,北京,100053

作者简介:

吕梦,女,博士研究生,研究方向为中医药防治心血管疾病。

通讯作者:

胡元会,男,教授,主任医师。研究方向为中医药防治心血管疾病。

中图分类号:

R73-34;R914

基金项目:

★?基金?项?目?:“优势病种-医院制剂-新药”研发专项(ZZ15-XY-LCO-02);中国中医科学院科技创新工程项目(CI2021A03801)。


Preparation and antitumor effects of andrographolide-modified compound J6
Author:
Affiliation:

Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing, 100053, China

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    摘要:

    目的 提供一种穿心莲内酯(AG)改构化合物J6的制备方法,并验证其抗肿瘤作用。方法 将AG与丙酸酐以≤72 mg∶5 mL的比例混合,在120~180 ℃条件下反应,将AG第3、14和19位的羟基修饰成丙酰基,得到AG改构化合物J6,通过13C NMR、1H NMR得到结构表征;通过CCK8实验检测J6对胃癌MKN45细胞、肾癌786O细胞、黑色素瘤A375细胞增殖的影响,并与AG对细胞增殖的作用进行对比。结果 CCK8结果显示,AG改构化合物J6能以时间及浓度依赖性抑制胃癌、肾癌、黑色素瘤细胞增殖,与AG相比,其抑制肿瘤的作用更显著。结论 本研究合成了一种AG改构化合物J6,可在更低的剂量范围内对胃癌MKN45细胞、肾癌786O细胞、黑色素瘤A375细胞发挥更高效的生长抑制作用,为抗肿瘤药物的研发提供了新思路。

    Abstract:

    Objective To provide a preparation method for andrographolide-modified compound J6 and to verify its antitumor effects.Methods Andrographolide was mixed with propionic anhydride in a ratio of ≤72 mg∶5 mL. At 120~180 ℃, andrographolide hydroxyl groups at positions 3, 14 and 19 were modified into propionyl groups to obtain andrographolide-modified compound J6 , which was structurally characterized by 13C NMR and 1H NMR. CCK8 assay was used to detect the effects of J6 on the proliferation of gastric cancer MKN45 cells, renal cancer 786O cells and melanoma A375 cells, and the effects of J6 on cell proliferation was compared with that of andrographolide.Results The results of CCK8 showed that andrographolide-modified compound J6 inhibited the proliferation of gastric cancer, renal cancer and melanoma cells in a time- and concentration-dependent manner. Compared with andrographolide, J6 showed a more significant inhibitory effect on tumor.Conclusion In this study, an andrographolide-modified compound J6 was synthesized. J6 can exert more efficient inhibition on the growth of gastric cancer MKN45 cells, kidney cancer 786O cells and melanoma A375 cells in a lower dose range, providing a new idea for the development of antitumor drugs.

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吕梦,朱雪萍,陈佳凡,尤雅萍,崔翰明,褚瑜光,师帅,胡元会.穿心莲内酯改构化合物J6的制备及抗肿瘤作用研究[J].肿瘤药学,2024,14(5):548-553 ( in Chinese)

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