半乳糖糖基化三氮唑马蹄金素衍生物的合成及抗乙肝病毒活性研究  

Synthesis and anti-HBV activity of galactopyranosyl derivatives of MTS with 1, 2, 3-triazole unit

作　　者：袁洁[1,2,3] 刘青川[4] 徐广灿[1,5] 胡占兴[1] 曾晓萍[1] 黄正明[4] 梁光义[1,5] 徐必学[1] 

机构地区：[1]贵州省中国科学院天然产物化学重点实验室,贵阳550002 [2]贵州大学药学院,贵阳550002 [3]新疆医科大学厚博学院,新疆克拉玛依834000 [4]中国人民解放军第三〇二医院,北京100039 [5]贵阳中医学院,贵阳550002

出　　处：《中南药学》2016年第5期457-464,共8页Central South Pharmacy

基　　金：国家自然科学基金(No.81360472)

摘　　要：目的设计合成具有肝靶向潜力的含1,2,3-三氮唑结构的肝靶向马蹄金素衍生物,以期提高药物在肝脏病变部位的浓度。方法以D-半乳糖、二缩三乙二醇、L-苯丙氨醇、L-酪氨酸甲酯盐酸盐等为起始原料,通过乙酰化、糖基化、环加成、缩合、水解等反应合成具有肝靶向潜力的含1,2,3-三氮唑结构的半乳糖糖基化MTS衍生物;采用Taq Man探针荧光定量PCR测定Hep G2 2.2.15细胞内HBV DNA含量以评价目标化合物抗HBV活性。结果设计合成了3个具有肝靶向潜力的含1,2,3-三氮唑结构的半乳糖糖基化MTS衍生物,并评价了其抗HBV活性。结论由于目标化合物在DMSO中溶解度极低,活性结果不佳。Objective To design and synthesize the potential hepatic targeting galactopyranosyl derivatives of MTS with 1, 2, 3-triazole unit to increase the drug concentration in liver lesion tissue. Methods Starting from D-galactose, triethylene glycol, L-phenylalaninol, L-tyrosine methyl ester hydrochloride etc., the potential he- patic targeting galactopyranosyl derivatives of MTS with l, 2, 3-triazole unit were synthesized via acetylation, glycosylation, cycloaddition, condensation, hydrolysis reaction and so on. The anti-HBV activities of the target compounds were evaluated with real-time PCR based on TaqMan probe to assay HBV DNA level in HepG2 2.2.15 cells. Results Three potential hepatic targeting galactopyranosyl derivatives of MTS with 1, 2, 3-triazole unit were synthesized and their anti-HBV activities were evaluated. Conclusion The anti-HBV activities of the target compounds are not ideal because of the low solubility of the compounds in DMSO.

关 键 词：肝靶向 半乳糖 1 2 3-三氮唑 马蹄金素衍生物 抗HBV活性 

分 类 号：R285[医药卫生—中药学]