2- and 6-methyl-1,4-naphthoquinone derivatives and potential bioreductive alkylating agents.
2- and 6-methyl-1,4-naphthoquinone derivatives and potential bioreductive alkylating agents.
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DOI：
10.1021/jm00348a023
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发表时间：
1982-06
影响因子：
7.3
通讯作者：
I. Antonini;T. Lin;L. A. Cosby;Y. Dai;A. Sartorelli
中科院分区：
文献类型：
--
作者：
I. Antonini;T. Lin;L. A. Cosby;Y. Dai;A. Sartorelli
许多烷化剂同时具有醌核和适当的取代基，使它们能够作为生物还原性烷化剂。为了开发具有独特性质的这类新化合物，我们合成了一系列2-和6-甲基-1，4-萘醌衍生物，并评价了它们对肉瘤180腹水细胞的抗肿瘤活性。这些醌类化合物中有几种具有抗肿瘤活性，能显著延长荷瘤小鼠的生存时间。活性最强的药剂是2-和6-甲基-1，4-萘醌的甲磺酸盐、甲苯磺酸盐和N-（氯乙基）氨基甲酸盐。这些试剂的作用机制可能涉及对醌甲基化物的生物还原活化，这一发现表明，具有最佳离去基团的化合物作为抑制剂最有效。
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.