Antonini I, Lin T S, Cosby L A, Dai Y R, Sartorelli A C
J Med Chem. 1982 Jun;25(6):730-5. doi: 10.1021/jm00348a023.
A number of antineoplastic agents possess both the quinone nucleus and an appropriate substituent that permits them to function as bioreductive alkylating agents. To develop new compounds of this type with unique properties, we have synthesized a series of 2- and 6-methyl-1,4-naphthoquinone derivatives and have evaluated them for antineoplastic activity against Sarcoma 180 ascites cells. Several of these quinones showed antitumor activity, causing significant prolongation of the survival time of tumor-bearing mice. Among the most active agents were the mesylates, tosylates, and N-(chloroethyl)carbamates of 2- and 6-methyl-1,4-naphthoquinone. That bioreductive activation to a quinone methide might be involved in the mechanism of action of these agents was shown by the finding that compounds with the best leaving groups were the most efficacious as antineoplastic agents.
许多抗肿瘤药物同时具有醌核和合适的取代基，这使得它们能够作为生物还原烷基化剂发挥作用。为了开发具有独特性质的此类新化合物，我们合成了一系列2-甲基和6-甲基-1,4-萘醌衍生物，并评估了它们对肉瘤180腹水癌细胞的抗肿瘤活性。其中几种醌显示出抗肿瘤活性，显著延长了荷瘤小鼠的存活时间。最具活性的药物包括2-甲基和6-甲基-1,4-萘醌的甲磺酸盐、对甲苯磺酸盐和N-(氯乙基)氨基甲酸盐。具有最佳离去基团的化合物作为抗肿瘤药物最有效，这一发现表明生物还原活化生成醌甲基化物可能参与了这些药物的作用机制。
