title: Semi-synthesis and biological evaluation of 1,2,3-triazole-based podophyllotoxin congeners as potent antitumor agents inducing apoptosis in HepG2 cells.
abstract: A series of 4β-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin congeners were synthesized by employing click chemistry and further evaluated for their antitumor activity by MTT assay. Among them, six congeners (10, 11, 12, 13, 22, and 24) exhibited approximately 100-fold more potent inhibitory activity against four tumor cell lines (HepG2, MKN-45, NCI-H1993, and B16) than etoposide as positive control. Docking studies on binding in the ATPase domain of topoisomerase II revealed perfect docking of four congeners in the active site. Furthermore, the podophyllotoxin congeners 10, 11, 12, and 13 induced cell cycle arrest of HepG2 cells at the G(2) /M phase in a concentration-dependent manner, assessed by flow cytometric analysis, highlighting that they exert their antitumor activity via HepG2 cell apoptosis.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, Sichuan, P. R. China.
authors.forename: Jinying
authors.initials: J
authors.lastname: Chen
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Ronghong
authors.initials: R
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Huijun
authors.initials: H
authors.lastname: Lai
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Guangcheng
authors.initials: G
authors.lastname: Wang
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Peng
authors.forename: Jingxiang
authors.initials: J
authors.lastname: Qiu
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.forename: Dong
authors.initials: D
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Ran
authors.forename: Aihua
authors.initials: A
authors.lastname: Peng
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D057930:Click Chemistry; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D014230:Triazoles; D011034:Podophyllotoxin