Design, synthesis, and biological evaluation of phosphoramide derivatives as urease inhibitors
Design, synthesis, and biological evaluation of phosphoramide derivatives as urease inhibitors
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DOI：
10.1021/jf072901y
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发表时间：
2008-05-28
影响因子：
6.1
通讯作者：
Garcia-Mina, Jose M.
中科院分区：
文献类型：
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作者：
Dominguez, Maria J.;Sanmartin, Carmen;Garcia-Mina, Jose M.
作为尿素酶抑制剂的磷酰胺衍生物的设计、合成和生物学评价已被开展以减少氨的损失。合成了40个磷衍生物，并评价了它们对菜豆尿素酶的抑制活性。此外，还进行了体内试验。所有化合物均经红外光谱、核磁共振氢谱、质谱图和元素分析确证。在某些情况下，进行了详细的分子模拟研究，这些研究突出了酶活性中心与化合物之间的相互作用，以及与它们作为尿素酶抑制剂的活性相关的特征。根据体外抑制活性的IC50值，12个化合物的IC50值低于1MU，其中8个化合物的活性比商品尿素酶抑制剂N-正丁基硫代磷三胺(NBPT)(100 NM)(AGROTAIN)有所提高。在活性结果和分子模拟研究结论的基础上，定义了新型潜在抑制剂的结构模型。
The design, synthesis, and biological evaluation of phosphoramide derivatives as urease inhibitors to reduce the loss of ammonia has been carried out. Forty phosphorus derivatives were synthesized and their inhibitory activities evaluated against that of jack bean urease. In addition, in vivo assays have been carried out. All of the compounds were characterized by IR, H-1 NMR, MS, and elemental microanalysis. In some cases, detailed molecular modeling studies were carried out, and these highlighted the interaction between the enzyme active center and the compounds and also the characteristics related to their activity as urease inhibitors. According to the IC50 values for in vitro inhibitory activity, 12 compounds showed values below 1 mu M and 8 of them represent improvements of activity in comparison to the commercial urease inhibitor N-n-butylthiophosphorictriamide (NBPT) (100 nM) (AGROTAIN). On the basis of the activity results and the conclusions of the molecular modeling study, a structural model for new potential inhibitors has been defined.