Structure-activity Relationships in the Development of Hypoxic Cell Radiosensitizers
| Autor: | R.S. Jacobs, R.G. Wallace, E.D. Clarke, G.E. Adams, M.E. Watts, P. Wardman, Ian J. Stratford, P. Gray, C.E. Smithen, J. Parrick |
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| Rok vydání: | 1979 |
| Předmět: |
Chronic exposure
Radiation-Sensitizing Agents Cell Survival Hypoxic cell Models Biological Redox Chinese hamster Structure-Activity Relationship Cricetulus Therapeutic index Cricetinae Metronidazole Animals Misonidazole Cytotoxicity Cells Cultured Dose-Response Relationship Drug biology Chemistry General Medicine biology.organism_classification In vitro Oxygen Nitroimidazoles Biophysics Regression Analysis |
| Zdroj: | International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine. 35:151-160 |
| ISSN: | 0020-7616 |
| DOI: | 10.1080/09553007914550161 |
| Popis: | This paper describes measurements of the aerobic cytotoxicity of 42 nitroaromatic and nitroheterocyclic compounds towards Chinese Hamster cells in vitro. The results of acute and chronic exposure were quantified, and the concentration C required to achieve a standard response estimated. Fitting the data to an equation of the form - log C = b0 + b1E, where E is the one-electron reduction potential, explained 47 and 71 per cent of the variance in the acute and chronic aerobic cytotoxicity respectively. The addition of further terms to the equation, quantifying partition properties, was not statistically significant. The coefficient b1 was similar for both acute and chronic exposure; the dependence of both cytotoxicity and radiosensitization efficiency on reduction potential was also similar. A therapeutic ratio derived from these in vitro measurements showed no dependence on redox or partition properties. The insensitivity of cytotoxicity and radiosensitization properties to variations in molecular structure, other than those which influence redox behaviour, offers exceptional flexibility in developing compounds of improved therapeutic ratio. |
| Databáze: | OpenAIRE |
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