Domínguez María J, Sanmartín Carmen, Font María, Palop Juan A, San Francisco Sara, Urrutia Oscar, Houdusse Fabrice, García-Mina José
Synthesis Section and Molecular Modeling Section, Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain.
J Agric Food Chem. 2008 May 28;56(10):3721-31. doi: 10.1021/jf072901y.
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, (1)H 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 IC(50) values for in vitro inhibitory activity, 12 compounds showed values below 1 microM 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.
为减少氨的损失，已开展了磷酰胺衍生物作为脲酶抑制剂的设计、合成及生物学评价。合成了40种磷衍生物，并评估了它们对刀豆脲酶的抑制活性。此外，还进行了体内试验。所有化合物均通过红外光谱、核磁共振氢谱、质谱和元素微量分析进行了表征。在某些情况下，还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脲酶抑制剂活性相关的特征。根据体外抑制活性的半数抑制浓度（IC50）值，12种化合物的值低于1微摩尔，其中8种与商业脲酶抑制剂N-正丁基硫代磷酸三酰胺（NBPT）（100纳摩尔）（AGROTAIN）相比活性有所提高。基于活性结果和分子模拟研究的结论，已定义了新的潜在抑制剂的结构模型。
