摘要
目的为提高五环三萜成分白桦醇的抗肿瘤活性,开发以白桦醇为先导物的抗肿瘤新药。方法在白桦醇C-3位或C-28位引入具有抗肿瘤作用的一氧化氮(NO)供体支链合成白桦醇单硝酸酯,并通过改性噻唑蓝(MTT)法测定衍生物对人源HepG2、HT-29、MCF-7等肿瘤细胞的体外抗肿瘤活性。结果合成了7个白桦醇单硝酸酯,所有化合物结构经红外光谱、核磁共振光谱、质谱进行确证,MTT结果显示所有衍生物对HT-29肿瘤细胞的抑制作用强于HepG2及MCF-7肿瘤细胞,其中化合物1g、1j对HT-29肿瘤细胞具有较强的选择性抑制作用。结论白桦醇C-3位或C-28位引入大空阻基团可能导致抗肿瘤活性下降,而C-3位引入含氮基团有利于提高抗肿瘤活性,可为白桦醇结构修饰的进一步研究提供参考。
Objective To improve the anti-tumor activity of pentacyclic triterpenoid and develop betulin derivatives as the new anti-tumor drugs.Methods Betulin mononitrates were synthesized by introducing NO donor moieties at C-3 or C-28 of betulin.The effects on the proliferation of HepG2,HT-29 and MCF-7 tumor cells in vitro were detected by MTT assay.Results The structures of seven betulin mononitrates were confirmed by IR,1H NMR,13C NMR and HR MS.MTT results showed anti-tumor activities of derivatives on HT-29 cells were stronger than those on HepG2 and MCF-7 tumor cells.Additionally,Compounds 1 g and 1 j showed strong inhibitory effects on HT-29 cells.Conclusion The introduction of a large steric hindrance groups at C-3 or C-28 of betulin may decrease anti-tumor activity,while the introduction of a nitrogen-containing group at C-3 is beneficial for its antitumor activity.
作者
何宝恩
罗璟
龙泳伶
肖敏捷
张特
王涛
HE Baoen;LUO Jing;LONG Yonglin;XIAO Minjie;ZHANG Te;WANG Tao(School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;Department of Pharmacy,Guangzhou Women and Children Medical Center,Guangzhou 510623 Guangdong,China;Foshan Women and Children Hospital,Foshan 528000 Guangdong,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2020年第11期1368-1372,共5页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
广东省高等教育教学改革项目(粤教高函180号)
广东省科技计划项目(2012A030100015)。
