Lake L M, Grunden E E, Johnson B M
Cancer Res. 1975 Oct;35(10):2858-63.
N-Demethylated metabolites of the antineoplastic agent hexamethylmelamine were synthesized, and their toxicities and antitumor activities were determined in vivo. Determinations of the lethal dose for 10% of the male C57BL X DBA/2 F1 (hereafter called BD2F1) mice showed hexamethylmelamine toxicity to be decreased by N-demethylation; the metabolites showed a direct relationship between potency (mmoles/kg/day) and number of methyl groups present. In BD2F1 mice bearing Sarcoma 180 or Lewis lung carcinoma, the antitumor activities of the methylmelamines decreased with a reduction in number of methyl groups, but were similar at equitoxic levels. Results were similar in L1210 leukemic mice treated with lethal dose levels of the metabolites for 10% of the mice when mean survival times were measured. The therapeutic equality produced with equitoxic levels, together with the ineffectiveness of melamine, suggested that the presence of a methyl group, rather than the number, was the determining factor in the antitumor activity of the methylmelamines.
合成了抗肿瘤药物六甲蜜胺的N-去甲基代谢物，并在体内测定了它们的毒性和抗肿瘤活性。对10%的雄性C57BL×DBA/2 F1（以下简称BD2F1）小鼠的致死剂量测定表明，N-去甲基化降低了六甲蜜胺的毒性；这些代谢物显示出效力（毫摩尔/千克/天）与存在的甲基数量之间存在直接关系。在携带肉瘤180或Lewis肺癌的BD2F1小鼠中，甲基蜜胺的抗肿瘤活性随着甲基数量的减少而降低，但在等效毒性水平下相似。当测量平均存活时间时，用代谢物的致死剂量水平处理L1210白血病小鼠，结果相似。等效毒性水平产生的治疗等效性，以及三聚氰胺的无效性，表明甲基的存在而非数量是甲基蜜胺抗肿瘤活性的决定因素。
