title: Design, synthesis, and anticancer activity of novel berberine derivatives prepared via CuAAC "click" chemistry as potential anticancer agents.
abstract: A series of novel derivatives of phenyl-substituted berberine triazolyls has been designed and synthesized via copper-catalyzed azide-alkyne cycloaddition click chemistry in an attempt to develop antitumor agents. All of the compounds were evaluated for anticancer activity against a panel of three human cancer cell lines, including MCF-7 (breast), SW-1990 (pancreatic), and SMMC-7721 (liver) and the noncancerous human umbilical vein endothelial cell (HUVEC) cell lines. The results indicated that most of the compounds displayed notable anticancer activities against the MCF-7 cells compared with berberine. Among these derivatives, compound 16 showed the most potent inhibitory activity against the SW-1990 and SMMC-7721 cell lines, with half-maximal inhibitory concentration (IC50) values of 8.54±1.97 μM and 11.87±1.83 μM, respectively. Compound 36 exhibited the most potent inhibitory activity against the MCF-7 cell line, with an IC50 value of 12.57±1.96 μM. Compound 16 and compound 36 exhibited low cytotoxicity in the HUVEC cell line, with IC50 values of 25.49±3.24 μM and 30.47±3.47 μM. Furthermore, compounds 14, 15, 16, 17, 18, 32, and 36 exhibited much better selectivity than berberine toward the normal cell line HUVEC.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China ; School of Pharmacy, FuJian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Tian-Hua
authors.initials: TH
authors.lastname: Yan
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yan
authors.affiliation: Diakite Biological Technology Co., Ltd, Shanghai, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Rui-Lian
authors.initials: RL
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Hu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Yuan-Ying
authors.initials: YY
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Qing-Yan
authors.initials: QY
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Cao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001599:Berberine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D057930:Click Chemistry / Q000379:methods; D015195:Drug Design; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D061986:MCF-7 Cells; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001599:Berberine
keywords: anticancer; berberine; click chemistry; structure–activity relationship