Design, Synthesis, and Biological Evaluation of Phosphoramide Derivatives as Urease Inhibitors
- 1 May 2008
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Agricultural and Food Chemistry
- Vol. 56 (10), 3721-3731
- https://doi.org/10.1021/jf072901y
Abstract
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.Keywords
This publication has 31 references indexed in Scilit:
- Urea, Fluorofamide, and Omeprazole Treatments Alter Helicobacter Colonization in the Mouse Gastric MucosaHelicobacter, 2006
- Contribution of dppA to Urease Activity in Helicobacter pylori 26695Helicobacter, 2005
- Structure-based rationalization of urease inhibition by phosphate: novel insights into the enzyme mechanismJBIC Journal of Biological Inorganic Chemistry, 2001
- The Protein Data BankNucleic Acids Research, 2000
- X‐ray Absorption Spectroscopy Study of Native and Phenylphosphorodiamidate‐Inhibited Bacillus pasteurii UreaseJBIC Journal of Biological Inorganic Chemistry, 1996
- Temperature and low concentration effects of the urease inhibitor N-(n-butyl) thiophosphoric triamide (nBTPT) on ammonia volatilization from ureaSoil Biology and Biochemistry, 1990
- Effect of Phenylphosphorodiamidate on Ammonia Volatilization as Affected by Soil Temperature and Rates and Distribution of UreaSoil Science Society of America Journal, 1987
- Effect of Phenylphosphorodiamidate on Immobilization and Ammonia VolatilizationSoil Science Society of America Journal, 1987
- Development and use of quantum mechanical molecular models. 76. AM1: a new general purpose quantum mechanical molecular modelJournal of the American Chemical Society, 1985
- Effectiveness of Phosphoroamides for Retardation of Urea Hydrolysis in SoilsSoil Science Society of America Journal, 1984