Design of β-carboline derivatives as DNA-targeting antitumor agents
| Autor: | Huaji Guan, Yan Ma, Rihui Cao, Xiaodong Liu, Anlong Xu, Hongsheng Chen, Wenlie Peng |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Antineoplastic Agents
In Vitro Techniques Sensitivity and Specificity HeLa Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Drug Discovery Tumor Cells Cultured medicine Humans Cytotoxic T cell Cytotoxicity Cell Proliferation Pharmacology Molecular Structure biology Cell Cycle Organic Chemistry Hydrogen Bonding Stereoisomerism DNA General Medicine Prodrug Flow Cytometry biology.organism_classification In vitro Mechanism of action chemistry Biochemistry Cell culture Drug Design Drug Screening Assays Antitumor medicine.symptom Carbolines HeLa Cells |
| Zdroj: | European Journal of Medicinal Chemistry. 41:1167-1179 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2006.05.004 |
| Popis: | This research studied the structure-activity relationship of β-carboline derivatives as antitumor agents, in which 41 synthesized compounds and their cytotoxicity to tumor and normal cell lines were assayed. It was proved that substituent in position-9 of the β-carboline ring could reinforce the DNA intercalating ability and consequently cytotoxicity to tumor cell lines, and the amidation of amino group at the end of the DNA targeting side chain in position-3 could cripple the DNA intercalating activity of these compounds, which resultingly initiated the cytotoxic selectivity to tumor cell lines rather than to normal ones. Furthermore, the S and G2-M arrest induced by these compounds confirmed that they could target DNA and lead to DNA destructions in Hela cells. In short, this study may provide a framework to design a novel antitumor drug that could surpass Adriamycin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect