Synthesis of 4β-triazole-podophyllotoxin derivatives by azide–alkyne cycloaddition and biological evaluation as potential antitumor agents

• DOI: 10.1016/j.ejmech.2011.07.024
• Publication Date: 2011-07-25T18:06:52Z
• Authors: Hong Chen; Song Zuo; Xiaochen Wang; Xiaowei Tang; Ming Zhao; Yanling Lu; Liting Chen; Jing Liu; Yongfeng Liu; Dailin Liu; Shi Zhang; Tan Li
• Keywords: Models, Molecular; Azides; Spectrometry, Mass, Electrospray Ionization; Magnetic Resonance Spectroscopy; Spectrophotometry, Infrared; Antineoplastic Agents; Triazoles; 01 natural sciences; 3. Good health; 0104 chemical sciences; Cyclization; Cell Line, Tumor; Humans; Drug Screening Assays, Antitumor; Podophyllotoxin

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.