薯蓣皂苷元氨基酸衍生物的制备及其抗肿瘤作用研究

摘要

Objective To synthesize the amino acid derivates of diosgenin, investigate the effect of derivates on inhibition of human tumor cell growth and study its antitumor mechanism preliminarily. Methods The derivates of amino acid from diosgenin were prepared by esterification reaction. The chemical structure of derivatives was determined by nuclear magnetic resonance (NMR) spectroscopy. The inhibitive effect of cell growth of derivatives was measured by MTT assay. Flow cytometic analysis was used to detect cell phase distribution of Caco-2 cell. Results Four amino acid derivatives from diosgenin were synthesized successfully, including phenylalanine, alanine, proline and valine diosgenin ester. Valine diosgenin ester was a new compound, and it had a clear growth inhibition in 4 tumor cell lines including Caco-2, MGC-709, SPC-A-1and SH-SY5Y in vitro, but the others had not. Caco-2 cells treated with valine diosgenin ester showed an obvious effect on the cell cycle, and an increase of cell in S phase and a decrease in G2/M phase were found.Conclusions Novel derivatives-valine diosgenin ester synthesized has an obvious growth inhibition effect to tumor cell lines in vitro, and it also has an effect on the cell cycle of Caco-2.%目的：制备薯蓣皂苷元氨基酸衍生物，考查衍生物的抗肿瘤作用，并初步探讨其作用机制。方法利用酯化反应制备衍生物，核磁检测确定衍生物化学结构，噻唑蓝(MTT)法检测衍生物对人肿瘤细胞增殖的抑制作用，利用流式细胞术检测缬氨酸薯蓣皂苷元酯对人结肠癌 Caco-2肿瘤细胞周期影响。结果成功制备了4个衍生物，分别为苯丙氨酸薯蓣皂苷元酯、丙氨酸薯蓣皂苷元酯、脯氨酸薯蓣皂苷元酯和缬氨酸薯蓣皂苷元酯，其中缬氨酸薯蓣皂苷元酯为新化合物，其对培养的人结肠癌 Caco-2、人胃腺癌 MGC-709、人肺腺癌细胞SPC-A-1和人神经母细胞瘤SH-SY5Y 4种细胞增殖均表现出明显的抑制作用，而另外3个衍生物抑制作用不明显。缬氨酸薯蓣皂苷元酯能明显影响Caco-2细胞周期，使S期细胞增加， G2/M期细胞减少。结论制备合成的新化合物缬氨酸薯蓣皂苷元酯在体外对人肿瘤细胞生长具有明显抑制作用，能明显影响Caco-2细胞周期。