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托米嗪——一种具有抗肿瘤活性的新型叶酸代谢酶抑制剂

[Tomizine--a new inhibitor of folate metabolism enzymes possessing an antitumor activity].

作者信息

Sokolova A S, Riabokon' N A, Ershova Iu A, Andreeva N A, Nemeriuk M P

出版信息

Vopr Onkol. 1975;21(11):45-50.

PMID:174306
Abstract

In the experiments on enzymic systems functioning in the metabolism of folic acid and on transplantable tumors in animals the preparation thomizine (chlorohydrate 4-methoxy-6-aminopyrimido (4,5-b) (1,4) thiazine) was worked out. Thomizine, as well as the known antimetabolite of folic acid-methotrexate, suppresses the activity of dihydrofolate reductase, but contrary to it suppresses FAP enzymic system, inhibiting aminopterin in the organism. Thomizine differes from methotrexate by another spectrum of antitumor effect, selective suppression of the tumor tissue growth, compared with the normal in vitro, it does not inhibit leucopoiesis, shows less toxicity and insignificant cumulative properties.

摘要

在关于叶酸代谢中起作用的酶系统以及动物可移植肿瘤的实验中,研制出了托米嗪制剂(4-甲氧基-6-氨基嘧啶并(4,5-b)(1,4)噻嗪氯水合物)。托米嗪与已知的叶酸抗代谢物甲氨蝶呤一样,能抑制二氢叶酸还原酶的活性,但与之相反的是,它能抑制机体中的氨基蝶呤,从而抑制FAP酶系统。托米嗪与甲氨蝶呤在抗肿瘤作用谱方面有所不同,它能选择性抑制肿瘤组织生长,与正常组织相比,在体外它不抑制白细胞生成,毒性较小且累积特性不明显。

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