Synthesis, hydroxyl radical production and cytotoxicity of analogues of bleomycin
| Autor: | Peter Wardman, John Parrick, Jackie A. Highfield, Lina K. Mehta |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cell Survival
medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Carboxamide Bleomycin Biochemistry Chemical synthesis chemistry.chemical_compound Cricetulus Cricetinae Drug Discovery medicine Animals Cytotoxicity Molecular Biology Hydroxyl Radical Organic Chemistry Prodrug In vitro chemistry Molecular Medicine Hydroxyl radical DNA |
| Zdroj: | Bioorganic & Medicinal Chemistry. 8:1065-1073 |
| ISSN: | 0968-0896 |
| Popis: | Two pyridine analogues of the metal complexing region of the anticancer drug bleomycin and two related but deactivated prodrugs have been linked to a 2,6-diphenylpyridine derivative as a DNA binding unit. The 2,6-diphenylpyridine system is structurally related to known amplifiers of the cytotoxicity of bleomycin. The conjugates were found to bind to DNA more strongly than bleomycin-A2 and were more cytotoxic than the corresponding compounds lacking the DNA binding unit. On exposure of a mixture of cells and prodrugs to hypoxia and then air, the prodrug containing the nitrohistidine unit was not bioreductively activated but the prodrug having an N-oxide group was bioreductively activated. This result represents a novel approach to the improvement of the therapeutic ratio of bleomycin analogues. |
| Databáze: | OpenAIRE |
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