title: Synthesis and cytotoxic activity of 3, 4, 11-trihydroxyl modified derivatives of bergenin.
abstract: 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 (1)H 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 doubly-substituted (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.
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: De-Biao
authors.initials: DB
authors.lastname: Yan
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Dong-Ping
authors.initials: DP
authors.lastname: Zhang
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China. Electronic address: liuwenyuan8506@163.com.
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Liu
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China. Electronic address: fengfeng@cpu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Bin
authors.initials: B
authors.lastname: DI
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Guo
authors.affiliation: Jiangxi Qingfeng Pharmaceutical Ltd., Ganzhou 341008, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xie
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D053958:Dipterocarpaceae / Q000737:chemistry*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013274:Stomach Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001578:Benzopyrans; D010936:Plant Extracts; C006741:bergenin
keywords: 3-, 4-, and/or 11-trihydroxyl modified derivatives; Bergenin; Cytotoxic activity; Structure-activity relationships