García E, Lopez-de-Cerain A, Garrido E, Gullón A, Monge A
Research Centre for Applied Pharmacobiology, University of Navarra, Pamplona, Spain.
Arzneimittelforschung. 1994 Aug;44(8):953-6.
The clastogenicity of four compounds of the series 3-(4'-substituted-benzylidenamino)5H-1,2,3-triazin [5,4-b]indol-4-one, which showed an important activity as inhibitors of platelet aggregation, has been evaluated. The compounds studied differed in the physicochemical properties of the substituent occupying the 4' position of the benzilidenamino group. The 4' substituents were: -H, -NO2, -OCH3 and -C6H5. They were tested on V-79 cells, both with and without metabolic activation, and structural chromosome aberrations were scored. Compounds with -H, -NO2 and -OCH3 radicals were active both with and without metabolic activation. Compound with -C6H5 radical was clastogenic only at the highest dose tested and with metabolic activation. It appears that the compound with the biggest and most hydrophobic substituent is the least clastogenic of the series. These results are in agreement with some previous ones obtained in bacteria and show a good correlation between the results of the Ames test and the structural chromosome aberrations test.
对3-(4'-取代苄叉氨基)-5H-1,2,3-三嗪并[5,4-b]吲哚-4-酮系列中的四种化合物进行了致断裂性评估，这些化合物作为血小板聚集抑制剂表现出重要活性。所研究的化合物在占据苄叉氨基4'位的取代基的物理化学性质上有所不同。4'位取代基分别为：-H、-NO₂、-OCH₃和-C₆H₅。在有和没有代谢活化的情况下，在V-79细胞上对它们进行了测试，并对结构性染色体畸变进行了评分。带有-H、-NO₂和-OCH₃基团的化合物在有和没有代谢活化的情况下均有活性。带有-C₆H₅基团的化合物仅在测试的最高剂量且有代谢活化时具有致断裂性。看来该系列中具有最大且最疏水取代基的化合物致断裂性最小。这些结果与先前在细菌中获得的一些结果一致，并且在艾姆斯试验结果与结构性染色体畸变试验结果之间显示出良好的相关性。
