Skov K A, Farrell N P
Int J Radiat Biol Relat Stud Phys Chem Med. 1987 Aug;52(2):289-97. doi: 10.1080/09553008714551751.
The radiosensitizer 2-amino-5-nitrothiazole (ANT) can react with platinum to form many products because of the availability of two potential nitrogen donors as ligands for metals. Two of these complexes, both with two ANT molecules in the trans configuration, differ because of their linkages. In the first, Pt is bound to ANT via the amine group (A) and in the second via the thiazole ring nitrogen (R). Isomer R is a better radiosensitizer than A in hypoxic Chinese hamster ovary cells, giving enhancement ratios of 1.6 versus 1.15 with 100 mumol dm-3 complex. The ring-bound isomer also exhibits higher toxicity than the amine bound in air and under conditions of hypoxia. Sensitization by isomer R is much higher under conditions of hypoxia than in air. In an assay to assess DNA binding, isomer R inhibited restriction enzyme cleavage of DNA but isomer A did not (up to 6 h at 300 mumol dm-3). It appears from this study on two very similar complexes that the complex which exhibits stronger binding may be targetting the radiosensitizer to the DNA, resulting in greatly improved sensitization.
放射增敏剂2-氨基-5-硝基噻唑（ANT）由于有两个潜在的氮供体作为金属配体，可与铂反应形成多种产物。其中两种配合物，反式构型中均有两个ANT分子，因其连接方式不同而有所差异。第一种中，铂通过胺基（A）与ANT相连；第二种中，铂通过噻唑环氮（R）与ANT相连。在缺氧的中国仓鼠卵巢细胞中，异构体R作为放射增敏剂比异构体A效果更好，100 μmol dm⁻³的配合物中，其增强比分别为1.6和1.15。在有氧和缺氧条件下，环连接的异构体毒性也比胺连接的异构体更高。异构体R在缺氧条件下的增敏作用比在有氧条件下高得多。在一项评估DNA结合的试验中，异构体R可抑制DNA的限制性酶切，而异构体A则不能（在300 μmol dm⁻³下长达6小时）。从对这两种非常相似的配合物的研究来看，结合更强的配合物可能将放射增敏剂靶向到了DNA上，从而极大地提高了增敏效果。
