Synthesis and evaluation of novel podophyllotoxin derivatives as potential antitumor agents
| Autor: | Zhong-Mei Zou, Zhong-Heng Zhang, Hong Chen, Wei-Hua Cheng, Bo Cao, Cong Niu, Li-Ming Zhang, Hai Shang, Shi Zhang, Dan-Li Tian |
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| Rok vydání: | 2014 |
| Předmět: |
DNA repair
Antineoplastic Agents Apoptosis Chemistry Techniques Synthetic Pharmacology HeLa Drug Discovery medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 RNA Messenger Cytotoxicity Etoposide P-glycoprotein Cell Proliferation Podophyllotoxin biology Chemistry Cell growth Organic Chemistry General Medicine biology.organism_classification Drug Resistance Multiple Multiple drug resistance Gene Expression Regulation Neoplastic biology.protein K562 Cells medicine.drug HeLa Cells |
| Zdroj: | European journal of medicinal chemistry. 85 |
| ISSN: | 1768-3254 |
| Popis: | Cancer multidrug resistance (MDR) is a common cause of treatment failure in cancer patients. Increased expression of permeability glycoprotein (P-gp), which is also known as MDR-1, is the main cause of multidrug resistance. Podophyllotoxin derivatives hold great promise in the battle to overcome multidrug resistance, as they can induce cytotoxicity through multiple mechanisms. Here, we synthesized sixteen novel podophyllotoxin derivatives and evaluated their cytotoxicities in human cancer cell lines, HeLa, K562 and K562/A02. Some of these compounds were more potent than etoposide, a clinically relevant inhibitor of DNA repair enzymes. In particular, compound 5p exhibited the most potent activity toward drug-resistant K562/A02 cells, as it robustly inhibited tumor cell proliferation and induced apoptosis. Furthermore, preliminary investigation suggested that 5p inhibited the expression of MDR-1 in K562/A02 cells more effectively than etoposide. |
| Databáze: | OpenAIRE |
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