3-硝基-1,2,4-三唑类乏氧细胞放射增敏剂的构效关系

为了寻找毒性低、增敏作用强的乏氧细胞放射增敏剂,设计并合成了一系列5-溴-,5-甲基-,和5-未取代的3-硝基-1,2,4-三唑-1-乙酰胺类化合物,用HeLaS3细胞进行了体外试验。结果表明5-溴取代衍生物的增敏作用强于相应的5-甲基-或5-未取代的硝基三唑衍生物,但是它们的毒性亦增大。修饰1位乙酰胺侧链也可以改变化合物的增敏作用和亲脂性。在所测定的化合物中TA-101[2-(3-硝基-1-三唑基)乙酰胺]由于有高的增敏作用和低亲脂性,可能是一个有希望的放射增敏剂。

STRUCTURE-ACTIVITYRELATIONSHIPSFOR3-NITRO-1,2,4-TRIAZOLES AS HYPOXIC TUMOR CELL RADIOSENSTIZER

In order to search for effective radiosensitizer of hypoxic cell with low toxicity,a series of 5-bromo-,5-methy1-,and 5-unsubstituted-3-nitro-1,2,4-triazole-1- acetamides were synthesized and tested in vitro with HeLa S3 cells.The radiosensitlzing activity of 5-bromo-derivatives are more potent than those of corresponding 5-methyl-or 5- unsubstituted-1,2,4-triazole derivatives,but the chronic aerobic cytotoxicities are increased.Modification of the N¹-acetamide side chain can also change the radiosensitizing activity and the lipophilicity.Among all the tested nitrotriazole derivatives,TA-101[2-(3- nitro-1-triazolyl)acetamide],may be a potential radiosensitizer because of its higher sensitizing activity and much lower lipophilicity.