Ferguson L R, Denny W A, Feigon J
Cancer Research Laboratory, University of Auckland Medical School, New Zealand.
Mutat Res. 1988 Sep;201(1):213-8. doi: 10.1016/0027-5107(88)90128-5.
The ability of proflavine (3,6-diaminoacridine) and its 2,7-dimethyl, 2,7-diethyl, 2,7-diisopropyl and 2,7-di-tert.-butyl derivatives to induce the 'petite' mutation in Saccharomyces cerevisiae has been studied in relation to the DNA-binding properties of the compounds. The nature of the binding has been investigated by nuclear magnetic resonance techniques, and the results support and clarify earlier suggestions that the first 3 members of the series intercalate into DNA while the diisopropyl and di-tert.-butyl compounds do not. Toxicity of the drugs was primarily associated with their mode of DNA binding, but lipophilicity had an important secondary effect. It seems likely that the toxic properties of the more lipophilic DNA-intercalating members of the series mask their potential for 'petite' mutagenesis.
已研究了原黄素（3,6 - 二氨基吖啶）及其2,7 - 二甲基、2,7 - 二乙基、2,7 - 二异丙基和2,7 - 二叔丁基衍生物诱导酿酒酵母“小菌落”突变的能力，并将其与化合物的DNA结合特性相关联。通过核磁共振技术研究了结合的性质，结果支持并阐明了早期的推测，即该系列的前三个成员可嵌入DNA，而异丙基和二叔丁基化合物则不能。药物的毒性主要与其DNA结合方式有关，但亲脂性也有重要的次要影响。该系列中亲脂性更强的DNA嵌入成员的毒性特性似乎掩盖了它们诱导“小菌落”突变的潜力。
