DNA-targeted 2-nitroimidazoles: in vitro and in vivo studies
| Autor: | Andrew M. Rauth, David S.M. Cowan, R. A. Mcclelland, J. F. Matejovic |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1994 |
| Předmět: |
Cancer Research
Misonidazole Radiation-Sensitizing Agents Nitro compound CHO Cells Biology In Vitro Techniques chemistry.chemical_compound Mice Structure-Activity Relationship In vivo Cricetinae Organoid Tumor Cells Cultured Animals chemistry.chemical_classification Mice Inbred C3H Phenanthridine Cytotoxins Chinese hamster ovary cell DNA In vitro Intercalating Agents Phenanthridines Organoids Oncology chemistry Biochemistry Solubility Nitroimidazoles Carcinoma Squamous Cell Cell Division Research Article |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | A series of compounds in which a 2-nitroimidazole is linked to a DNA intercalating phenanthridine moiety has been synthesised. Previously, three such compounds, termed nitroimidazole-linked phenanthridines or NLPs, were tested in vitro and showed a greatly enhanced molar efficiency as hypoxic cell radiosensitisers and cytotoxins compared with the untargeted 2-nitroimidazole, misonidazole. Since the cytoxicity of these compounds was shown to be inversely proportional to linker chain length while radiosensitising ability was dependent of it, compounds with five and six carbons in the chain were synthesised in an attempt to lower the toxicity of the drugs while increasing their ability to 'scan' DNA for target radicals. These compounds and a comparison series of n-alkylated phenathridinium ions have been characterised and evaluated in vitro using Chinese hamster ovary and V79 cells and their effects compared with misonidazole. Based on in vitro results, one member of the series was selected and evaluated in vitro using a V79 spheroid tumour model and in vivo using an SCCVII transplantable tumour system. These studies have demonstrated the potential utility of this class of compound. |
| Databáze: | OpenAIRE |
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