Semi-Synthesis and Biological Evaluation of 1,2,3-Triazole-Based Podophyllotoxin Congeners as Potent Antitumor Agents Inducing Apoptosis in HepG2 Cells
| Autor: | Huijun Lai, Ronghong Zhang, Yan Ran, Jun Wang, Aihua Peng, Tao Chen, Jingxiang Qiu, Fei Peng, Jie Tang, Yuquan Wei, Guangcheng Wang, Lijuan Chen, Liang Ma, Xiaolin Liang, Jinying Chen, Qinyuan Xu, Dong Cao |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Cell cycle checkpoint
Pharmaceutical Science Antineoplastic Agents Pharmacology Biology Inhibitory Concentration 50 Structure-Activity Relationship Drug Discovery medicine Humans Structure–activity relationship MTT assay Etoposide Podophyllotoxin Molecular Structure Topoisomerase Cell Cycle Hep G2 Cells Triazoles Cell cycle Molecular Docking Simulation Biochemistry Docking (molecular) biology.protein Click Chemistry Drug Screening Assays Antitumor medicine.drug |
| Zdroj: | Archiv der Pharmazie. 345:945-956 |
| ISSN: | 0365-6233 |
| DOI: | 10.1002/ardp.201100438 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text