Kawazoe Y, Tamura N
Gan. 1981 Dec;72(6):862-7.
New hydrophilic alkylating agents, isethionic acid esters, are proposed for use as synthetic biological alkylating agents. Methyl, ethyl, and isopropyl esters of isethionic acid were synthesized starting from isethionate and the corresponding alkyl bromides or iodides in good yields. This synthetic procedure might be generally applicable to syntheses of alkyl isethionates. The derivatives thus prepared were water-soluble, as expected, and their alkylating abilities were very similar to those of the corresponding methanesulfonates. Hence, isethinonic acid esters might be suitable for use as hydrophilic biological alkylating agents in place of methanesulfonates. In order to determine the effectiveness of isethionates as anticancer alkylating agents, 1,4-butanediol diisethionate was prepared as a model compound and its anticancer activities against adenocarcinoma 755, sarcoma 180, L1210, and P388 were compared with those of the corresponding methanesulfonate, busulfan. The isethionate was superior to busulfan in all the assay systems employed. 1,5-Pentanediol diisethionate was also prepared and assayed. The results were similar to those for the 1,4-butanediol analog. In conclusion, in the design of molecules for use as cancer chemotherapeutics, the isethionic acid ester group is worth considering, and may be preferable to other commonly used leaving groups, including methanesulfonic acid ester.
新型亲水性烷基化剂——羟乙磺酸酯，被提议用作合成生物烷基化剂。以羟乙磺酸盐和相应的烷基溴或烷基碘为原料，合成了羟乙磺酸的甲酯、乙酯和异丙酯，产率良好。该合成方法可能普遍适用于羟乙磺酸烷基酯的合成。由此制备的衍生物如预期般具有水溶性，且其烷基化能力与相应的甲磺酸盐非常相似。因此，羟乙磺酸酯可能适合用作亲水性生物烷基化剂来替代甲磺酸盐。为了确定羟乙磺酸盐作为抗癌烷基化剂的有效性，制备了1,4 - 丁二醇二羟乙磺酸盐作为模型化合物，并将其对腺癌755、肉瘤180、L1210和P388的抗癌活性与相应的甲磺酸盐——白消安进行了比较。在所有使用的检测系统中，羟乙磺酸盐均优于白消安。还制备并检测了1,5 - 戊二醇二羟乙磺酸盐。结果与1,4 - 丁二醇类似物的结果相似。总之，在设计用作癌症化疗药物的分子时，羟乙磺酸酯基团值得考虑，并且可能比包括甲磺酸酯在内的其他常用离去基团更具优势。
