Synthesis and cytotoxic activity of 3, 4, 11-trihydroxyl modified derivatives of bergenin  

作　　者：YAN De-Biao ZHANG Dong-Ping LI Ming LIU Wen-Yuan FENG Feng DI Bin GUO Qing-Long XIE Ning 

机构地区：[1]Department of Natural Medicinal Chemistry, China Pharmaceutical University [2]Department of Pharmaceutical Analysis, China Pharmaceutical University [3]Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University [4]Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University [5]Jiangxi Qingfeng Pharmaceutical Ltd.

出　　处：《Chinese Journal of Natural Medicines》2014年第12期929-936,共8页中国天然药物（英文版）

基　　金：supported by the Natural Science Foundation of China(Nos.81274064 and 81373956);the National Fund for Fostering Talents of Basic Science(NFFTBS)(No.J1030830);the Science and Technology Supporting Project of Xinjiang(No.201291160)

摘　　要：To synthesize a series of 3-, 4-, and/or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro. The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzyl bromide. Treatment of dibenzyl bergenin with the corresponding acid in the presence of EDC·HCl and DMAP in CH2Cl2, followed by hydrogenation over Pd/C catalysts, afforded derivatives of bergenin esters. All of the target compounds were identified by IR, MS, and 1H NMR. Twenty-six novel and three known derivatives of bergenin esters were synthesized. Their cytotoxicity values were evaluated by the MTT assay on the inhibition of DU-145 and BGC-823 cells in vitro. Several triply-substituted(3a, 4a, 5a, 6a, 7a) and doublysubstituted(8b, 9b) bergenin derivatives exhibited higher cytotoxic activity than bergenin. The result showed that the size of substituents and the lipophilicity of the bergenin esters displayed an important role on their cytotoxic activity.To synthesize a series of 3-, 4-, and/or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro. The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzyl bromide. Treatment of dibenzyl bergenin with the corresponding acid in the presence of EDC·HCl and DMAP in CH2Cl2, followed by hydrogenation over Pd/C catalysts, afforded derivatives of bergenin esters. All of the target compounds were identified by IR, MS, and ^1H NMR. Twenty-six novel and three known derivatives of bergenin esters were synthesized. Their cytotoxicity values were evaluated by the MTT assay on the inhibition of DU-145 and BGC-823 cells in vitro. Several triply-substituted （3a, 4a, 5a, 6a, 7a） and doublysubstituted （8b, 9b） bergenin derivatives exhibited higher cytotoxic activity than bergenin. The result showed that the size of substituents and the lipophilicity of the bergenin esters displayed an important role on their cytotoxic activity.

关 键 词：BERGENIN 3- 4- and/or 11-trihydroxyl modified derivatives Cytotoxic activity Structure-activity relationships 

分 类 号：R284[医药卫生—中药学]