摘要
目的：合成新型的齐墩果酸-α-氨基膦酸酯衍生物,并研究其抗肿瘤活性.方法：以齐墩果酸为原料,经乙酰化反应后,与草酰氯反应成酰氯,继而在三乙胺作为缚酸剂的条件下,与α-氨基膦酸酯进行反应,一共合成了9个齐墩果酸-α-氨基膦酸酯衍生物,并对其结构进行表征.采用体外抗肿瘤活性测试MTT法,在细胞培养密度为2～3×104个/mL,药物测试浓度为50 μmol·L-1,作用时间为48 h条件下测试合成的齐墩果酸-α-氨基膦酸酯衍生物对人肺癌细胞A549、人肝癌细胞HepG-2、人宫颈癌细胞Hela和人乳腺癌细胞MDA-MB-231的增殖抑制活性.结果：这些化合物对受试肿瘤细胞株表现出不同程度的抑制活性.其中化合物2,4,7,10对人肺癌细胞A549和人宫颈癌细胞Hela具有显著的增殖抑制活性（对A549的抑制率分别为87.5％,85.3％,87.1％,87.8％,对Hela的抑制率分别为85.7％,78.7％,83.6％,87.9％）;化合物2和10对人乳腺癌细胞MDA-MB-231的增殖抑制活性很好（抑制率分别为82.0％,88.1％）.结论：这些齐墩果酸-α-氨基膦酸酯衍生物表现出不同程度的抗肿瘤活性,其中,苯环上邻位有卤素取代的齐墩果酸-α-氨基膦酸酯衍生物对测试细胞的增殖抑制活性较好.
Objective：To synthesize and evaluate anti-tumor activity of oleanolic acid-α-aminophosphonate derivatives.Method：Oleanolic acid-α-aminophosphonate derivatives were synthesized from oleanolic acid,which was treated by acetylation,then the acetylated product was reacted with oxalyl chloride,followed by esterification with α-aminophosphonate under triethylamine to obtain nine target compounds.The structures of these compounds were identified.MTT method was used to assay the anti-tumor activity of synthesized compounds against human lung cancer cell lines A549,human hepatic cell lines HepG-2,human cervical carcinoma cell lines Hela and human breast cancer cell lines MDA-MB-231.The density of cell culture was 2-3 × 104/mL,the concentration of drug was 50 μmol · L-1 for 48 hours.Result：These target compounds showed varying degrees of inhibitory activity against tumor cell lines.Compounds 2,4,7 and 10 exhibited significant inhibitory activity against human lung tumor cell A549 and human cervical carcinoma Hela （the inhibition rate against A549 was respectively 87.5％,85.3％,87.1％ and 87.8％; the inhibition rate against Hela was respectively 85.7％,78.7％,83.6％ and 87.9％）.Compounds 2 and 10 showed high inhibitory activity against human breast tumor cell MDA-MB-231 （the inhibition rate was respectively 82.0％ and 88.1％）.Conclusion：These oleanolic acid-α-aminophosphonate derivatives exhibited varying degrees of inhibitory activity against tumor cell lines.The compounds with ortho-substituted by halogen in phenyl ring showed better inhibitory activity.
出处
《中国实验方剂学杂志》
CAS
北大核心
2014年第8期123-128,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家重点基础研究计划(973计划)前期研究专项(2011CB512005)
广西自然科学基金项目(2011GXNSFD018010
2013GXNSFBA019184)
广西教育厅科研项目(201202ZD008)
广西师范大学校重点项目(2010ZD008)
药用资源化学与药物分子工程教育部重点实验室课题(CMEMR2012-B03
CMEMR2013-A01
CMEMR2013-C02)
广西医药产业人才小高地项目(1109)
