Comparative in vitro studies of Tiazofurin and a selenazole analog.
Comparative in vitro studies of Tiazofurin and a selenazole analog.
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噻唑呋林和硒唑类似物的体外比较研究。
DOI：
10.1016/s0006-291x(83)80179-x
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发表时间：
1983
影响因子：
3.1
通讯作者：
Robins,RK
中科院分区：
文献类型：
--
作者：
Streeter,DG;Robins,RK
2-β- d -核糖呋喃基硒代唑-4-羧酰胺是抗肿瘤药物Tiazofurin的硒代类似物，对培养的小鼠肿瘤细胞的细胞毒性比Tiazofurin高数倍。与Tiazofurin一样，硒唑类似物的细胞毒性被外源性鸟苷逆转，并且在培养的P388细胞中，这两种核苷特异性地抑制IMP脱氢酶的活性。这种抑制的剂量依赖性与两种药物的相对细胞毒性相关，表明硒化唑类似物对IMP脱氢酶更有效的抑制是其细胞毒性增加的主要原因。讨论了硒唑类似物的潜在代谢物对分离酶的特异性抑制作用。
2-β-D-Ribofuranosylselenazole-4-carboxamide, a selenazole analog of the antitumor agent Tiazofurin, is severalfold more cytotoxic to murine tumor cells in culture than Tiazofurin. Like Tiazofurin, the cytotoxicity of the selenazole analog is reversed by exogenous guanosine, and both nucleosides specifically inhibit IMP dehydrogenase activity in cultured P388 cells. The dose-dependency for this inhibition correlates with the relative cytotoxicities of both drugs, indicating that a more potent inhibition of IMP dehydrogenase by the selenazole analog is primarily responsible for its increased cytotoxicity. The specific inhibition of the isolated enzyme by potential metabolites of the selenazole analog is discussed.