title: Synthesis of 4β-triazole-podophyllotoxin derivatives by azide-alkyne cycloaddition and biological evaluation as potential antitumor agents.
abstract: A representative synthetic process of derivatizing the natural product podophyllotoxin utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is described including molecular design, reaction optimization and X-ray structure confirmation. Evaluation of cytotoxicity against human cancer cell lines (Hela, K562 and K562/A02) using MTT assay proves that these triazole derivatives have good antitumor activities. High activities toward the drug resistant K562/A02 cell line reveal promising future for these derivatives. The rarely prepared 1,5-disubstituted triazole isomers, which would be omitted by the "click chemistry", were found to have superior cytotoxicities to that of the 1,4-disubstituted isomers.
authors.affiliation: Pharmacognosy Division, Medical College of Chinese People's Armed Police Force, Tianjin 300162, China. chenhongtian06@yahoo.com.cn
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Song
authors.initials: S
authors.lastname: Zuo
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Tang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Yanling
authors.initials: Y
authors.lastname: Lu
authors.forename: Liting
authors.initials: L
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Dailin
authors.initials: D
authors.lastname: Liu
authors.forename: Shi
authors.initials: S
authors.lastname: Zhang
authors.forename: Tan
authors.initials: T
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001386:Azides / Q000737:chemistry; D045744:Cell Line, Tumor; D003500:Cyclization; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011034:Podophyllotoxin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001386:Azides; D014230:Triazoles; D011034:Podophyllotoxin