3-硝基三氮唑类衍生物体外放射增敏作用的生物学评价

A biological evaluation on in vitro radiosensitization of nitrotriazole derivatives.

探讨３－硝基三氮唑衍生物的放射增敏作用，并对其生物学效应作出评价。方法本文用克隆形成法研究了２２个３－硝基－１，２，４－三氮唑衍生物的体外放射增敏活性和乏氧、富氧细胞毒性。结果两个化合物的活性胜过ＭＩＳＯ，有三个化合物与ＭＩＳＯ和ＳＲ－２５０８相当，其余的其活性均较低。３－硝基三唑衍生物也像２－硝基咪唑类那样，其放射增敏活性与电子亲和性（用半波还原电位Ｅ１／２表示）有关。亲和性越大，即Ｅ１／２值越偏正，增敏活性越强。环核Ｎ１位和５位上取代基的结构和性质影响着化合物的Ｅ１／２、分配系数ｐ和细胞毒性。结论３－硝基三唑衍生物对乏氧和富氧（空气）细胞的毒性差别是很有限的，所以它们不是有效的乏氧调节细胞毒剂。但某些的放射增敏作用是值得深入研究的。

bjective\ To assess the radiosensitization of nitrotriazole derivatives and elucidate the structure activity relationships within this group of compounds. Method\ The partition coefficient (p), reduction potential (E 1/2 ),cytotoxicity and sensitization activity were determined by HPLC, polarography and colony formation, respectively. Results\ It was found that among these 22 derivatives,two compounds were more efficient than MISO,and other three were of the same efficiency as MISO was in radiosensitizing hypoxic cells,the rest showed poor radiosensitizing properties.As 2 nitroimidazoles,the radiosensitizing activity of a 3 nitrotriazole derivative correlates with its electron affinity,determined as E 1/2 ,half wave reduction potential.The greater is the electron affinity i.e.the more positive the E 1/2 ,the greater is the radiosensitizing efficiency.The value of E 1/2 ,partition coefficient p value and cytotoxicity of a nitrotriazole derivative are influenced by the structure and chemical properties of the substituent at N 1 or 5 position of triazole ring.The nitrotriazoles examined show only limited defferential hypoxic:aerobic toxicity. Conclusion\ Although the nitrotriazole derivative are not viable hypoxia mediated cytotoxins, the radiosensitization of some of them should be studied thoroughly.