一种雄烯二酮衍生物的合成及应用研究

Synthesis and Application of the Androstenedione Derivative

目的:提供一种雄烯二酮衍生物的合成方法,并对该化合物的应用进行研究。方法:以依西美坦和多聚甲醛为原料,二甲胺盐酸盐为催化剂,一步反应制备得到目标化合物——6,16-二亚甲基雄甾-1,4-二烯-3,17-二酮,优化反应条件,并通过气相色谱-质谱、核磁共振等表征确认结构。同时,对该化合物的体外抗肿瘤活性进行实验,选用细胞株为胃癌细胞株(MKN45)、肺癌细胞(HCC-78)、人乳腺癌细胞(MDA-MB-231)、肝癌细胞(HepG2)、卵巢癌细胞(3AO)。结果:通过表征确认了目标化合物的结构,且该化合物对肿瘤细胞有抑制活性,其中对人乳腺癌细胞(MDA-MB-231)和卵巢癌细胞(3AO)抑制效果较好。结论:提供了一条操作简单、成本低、收率高的6,16-二亚甲基雄甾-1,4-二烯-3,17-二酮合成路线,该化合物对肿瘤细胞有明显的抑制作用。

Objective:To provide a synthesis method of androstenedione derivatives,and to study the application of this compound.Methods:Using exemestane and paraformaldehyde as raw materials and dimethylamine hydrochloride as catalyst,the target compound——6,16-dimethylandrost-1,4-diene-3,17-dione was prepared by one-step reaction.The reaction conditions were optimized,and the structure was confirmed by gas chromatography-mass spectrometry,nuclear magnetic resonance and other characterizations.At the same time,the in vitro antitumor activity of the compound was tested,and the selected cell lines were gastric cancer cell line(MKN45),lung cancer cell(HCC-78),human breast cancer cell(MDA-MB-231),liver cancer cell(HepG2),and ovarian cancer cells(3AO).Results:The structure of the target compound was confirmed by characterization,and the compound had inhibitory activity on tumor cells,among which the inhibitory effect on human breast cancer cells(MDA-MB-231)and ovarian cancer cells(3AO)was better.Conclusions:It provides a simple,low cost and high yield synthesis route of 6,16-methylandrostere-1,4-diene-3,17-dione,which has obvious inhibitory effect on tumor cells.