Novel 4 beta-anilino-podophyllotoxin derivatives: design synthesis and biological evaluation as potent DNA-topoisomerase II poisons and anti-MDR agents
| Autor: | Yongzhou Hu, Danqing Xu, Wenting Du, Shijing Qian, Bo Yang, Chunqi Hu, Jianshu Lou, Li Wang, Qiaojun He |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
ATP Binding Cassette Transporter
Subfamily B Apoptosis Pharmacology Mice In vivo Cell Line Tumor Neoplasms medicine Potency Animals Humans Topoisomerase II Inhibitors ATP Binding Cassette Transporter Subfamily B Member 1 Enzyme Inhibitors Molecular Biology Etoposide P-glycoprotein Podophyllotoxin Aniline Compounds biology Chemistry Cell Cycle Xenograft Model Antitumor Assays Multiple drug resistance Cell culture biology.protein Topoisomerase-II Inhibitor Drug Screening Assays Antitumor Biotechnology medicine.drug |
| Zdroj: | Molecular bioSystems. 6(2) |
| ISSN: | 1742-2051 |
| Popis: | A new series of 4 beta-anilino-podophyllotoxin analogs have been designed, synthesized and evaluated their bioactivities as novel DNA-topoisomerase II poisons as well as P-glycoprotein (P-gp)-dependent multidrug resistance (MDR) inhibitors. The new compounds show improved potency and efficacy with respect to the parent molecule etoposide (VP-16), one of the semisynthetic derivatives of podophyllotoxin. The treatment of 5k-n in KB/VCR cells caused G(2)/M phase arrest and finally induced apoptosis. Furthermore, molecular docking is applied to testify that 5k-n could not be the substrates of P-gp, which is consistent with the result of MDR1 and P-glycoprotein express tests. The most potent compound 5n is chosen for in vivo studies, the administration of 5n was effective in treatment of cancer with a lower dose than VP-16 in drug-sensitive xenograft model and drug-resistant xenograft model. Compound 5n is a potential drug candidate for anticancer chemotherapy. |
| Databáze: | OpenAIRE |
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