Latent inhibitors. Part 8. Synthesis and evaluation of some mechanism-based inhibitors of dihydrofolate reductase
Latent inhibitors. Part 8. Synthesis and evaluation of some mechanism-based inhibitors of dihydrofolate reductase
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DOI：
10.1039/p19920001299
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发表时间：
1992
期刊：
影响因子：
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通讯作者：
J. Mcgill;L. Rees;C. Suckling;H. Wood
中科院分区：
文献类型：
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作者：
J. Mcgill;L. Rees;C. Suckling;H. Wood
合成了两种新的蝶啶-7-螺环丙烷，它们是二氢叶酸还原酶的时间依赖性不可逆抑制剂。一些相关的化合物包括环丙基取代喹啉和2-氨基蝶啶-4(3H),6(5H)-二酮也被制备，但这些化合物没有发现是时间依赖性抑制剂。使用几种二氢叶酸还原酶、大肠杆菌RT/39、两种大肠杆菌酶突变体、干酪乳杆菌和鸡肝来评估这些抑制剂。对所有酶均有活性，但对大肠杆菌野生型酶活性最强。
The synthesis of two new pteridine-7-spirocyclopropanes that are time-dependent irreversible inhibitors of dihydrofolate reductase is described. Several related compounds including a cyclopropyl substituted quinoxaline and 2-aminopteridine-4(3H),6(5H)-dione were also prepared but these compounds were not found to be time-dependent inhibitors. The inhibitors were assessed using several dihydrofolate reductases, Escherichia coli RT/39, two mutants of the E. coli enzyme, Lactobacillus casei, and chicken liver. Activity was found against all enzymes tested but most strongly against E. coli wild type enzyme.