Structure-activity relationships in the development of hypoxic cell radiosensitizers. I. Sensitization efficiency
| Autor: | I. R. Flockhart, E.D. Clarke, R.S. Jacobs, G.E. Adams, Raymond G. Wallace, J. Parrick, M.E. Watts, C.E. Smithen, Ian J. Stratford, D.S. Sehmi, P. Wardman |
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| Rok vydání: | 1979 |
| Předmět: |
Octanol
Radiation-Sensitizing Agents Cell Survival Nitrofurans Analytical chemistry Hypoxic cell Redox Models Biological Radiation Tolerance Chinese hamster Nitrobenzene chemistry.chemical_compound Structure-Activity Relationship Cricetulus Cricetinae medicine Partition (number theory) Animals Sensitization Cells Cultured Nitrobenzenes Chromatography biology Dose-Response Relationship Drug X-Rays General Medicine biology.organism_classification Nitro Compounds Partition coefficient Oxygen medicine.anatomical_structure chemistry Nitroimidazoles Regression Analysis |
| Zdroj: | International journal of radiation biology and related studies in physics, chemistry, and medicine. 35(2) |
| ISSN: | 0020-7616 |
| Popis: | The efficiency of 35 nitroaromatic and nitroheterocyclic compounds in radiosensitizing hypoxic Chinese Hamster cells in vitro was determined. The concentration C of the compound required to achieve an enhancement ratio of 1.6 was measured, and the redox and partition properties were quantified as the one-electron reduction potential at pH 7, E, and the octanol: water partition coefficient, P, respectively. Most of the compounds studied were 2-nitroimidazoles, but some 4- and 5-nitromidazoles, 5-nitrofurans and nitrobenzenes were investigated for comparison. Together with data for nine nitroimidazoles previously reported, the results were fitted to a structure-activity relationship of the form -log C = b0 + b1E + b2 log P + b3 (log P)2 using multiple linear regression analysis. Statistical tests showed that the coefficients b2 and b3 were not significantly different from zero and the simpler equation, obtained by omitting the terms in log P, explained 85 per cent of the variance in log C. Earlier reports that the radiosensitization efficiency of nitro compounds in vitro largely depends on the reduction potential were confirmed. The conclusive demonstration that P is unimportant in vitro is valuable in interpreting the results of experiments in vivo, where P is expected to have a much greater influence on biological response. |
| Databáze: | OpenAIRE |
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