title: Synthesis and anticancer activity of a novel series of 9-O-substituted berberine derivatives: a lipophilic substitute role.
abstract: To alter its hydrophobicity, a series of compounds bearing 9-O-alkyl- or 9-O-terpenyl- substituted berberine were synthesized and evaluated for anticancer activity against human cancer HepG2 and HT29 cell lines. We found that the lipophilic substitute of 9-O-alkyl- and 9-O-terpenyl berberine derivatives plays a role in inhibiting the human cancer cell growth and its activity could be maximized with the optimized substitute type and chain length. Most strikingly, nonetheless, of the six compounds prepared, sample 8, a farnesyl 9-O-substituted berberine, showed either comparable or better cytotoxic activity against human cancer HepG2 cell line than that of berberine. Compound 8 had also shown a 104-fold antiproliferation activity in compare with berberine against human hepatoma HepG2 cell lines after 48 incubation hours. Further, in Hoechst 33258 and annexin V-FITC/PI staining analyses it induced apoptosis in HepG2 cells at lower concentration than that of berberine for 24h. Take all; farnesyl 9-O-substituted berberine could be a potential candidate for new anticancer drug development.
authors.affiliation: Department of Food Science, College of Life Sciences, National Chiayi University, Taiwan, ROC.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Lo
authors.forename: Lin-Chen
authors.initials: LC
authors.lastname: Hsu
authors.forename: Min-Shin
authors.initials: MS
authors.lastname: Chen
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: Lin
authors.forename: Lih-Geeng
authors.initials: LG
authors.lastname: Chen
authors.forename: Cheng-Deng
authors.initials: CD
authors.lastname: Kuo
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001599:Berberine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D013329:Structure-Activity Relationship
chemical_list: C581254:9-O-farnesylberberine; D000970:Antineoplastic Agents; D001599:Berberine