潜在的放射增敏剂。4. 2-硝基咪唑核苷。

Potential radiosensitizing agents. 4. 2-Nitroimidazole nucleosides.

作者信息

Sakaguchi M, Webb M W, Agrawal K C

出版信息

J Med Chem. 1982 Nov;25(11):1339-42. doi: 10.1021/jm00353a013.

Abstract

A series of 2-nitroimidazole nucleoside analogues has been synthesized as potential radiosensitizers in an effort to reduce neurotoxicity and increase therapeutic efficacy. The 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl and glucothiopyranosyl analogues of 2-nitroimidazole were synthesized by condensation in the presence of stannic chloride and mercuric cyanide. The deacetylation of these esters was carried out with sodium methoxide at 0 degree C. Condensation of the trimethylsilyl derivative of 2-nitroimidazole with methyl 2-deoxy-2-chloro-4,7,8,9-tetra-O-acetyl-N-acetyl-alpha-D-neuraminate was achieved in the presence of mercuric bromide. These agents were tested for cytotoxicity and radiosensitization in vitro against Chinese hamster (V-79) cells under oxic and hypoxic conditions. The thioglucose and sialic acid analogues were found to be active radiosensitizers.

摘要

为了降低神经毒性并提高治疗效果，已合成了一系列2-硝基咪唑核苷类似物作为潜在的放射增敏剂。2-硝基咪唑的2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖基和硫代吡喃葡萄糖基类似物是在氯化锡和氰化汞存在下通过缩合反应合成的。这些酯的脱乙酰反应在0℃下用甲醇钠进行。2-硝基咪唑的三甲基硅烷基衍生物与2-脱氧-2-氯-4,7,8,9-四-O-乙酰基-N-乙酰基-α-D-神经氨酸甲酯在溴化汞存在下实现缩合。在有氧和缺氧条件下，对这些试剂进行了体外细胞毒性和对中国仓鼠（V-79）细胞的放射增敏作用测试。发现硫代葡萄糖和唾液酸类似物是有活性的放射增敏剂。