Synthesis and antitumor effect of new biological alkylating agents, isethionic acid esters.
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.
D000476:Alkanesulfonates / Q000138:chemical synthesis*; D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002066:Busulfan / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005260:Female; D007513:Isethionic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy
D000476:Alkanesulfonates; D000970:Antineoplastic Agents; D007513:Isethionic Acid; D002066:Busulfan