Synthesis, physico-chemical properties and biological activity of 3-(aminophenyl)propionic and 2-amino-2-phenyl butyric acid hexafluosilicates

Abstract

It is known that dental caries is a serious problem for the health care systems of most countries of the world, and the search for new effective and safe means of treatment and prevention of caries remains an urgent task of modern pharmaceutical science. At the same time, fluoride preparations remain the most effective and widely used in the modern arsenal of means for fighting caries. In recent years, ammonium hexafluorosilicates have been actively studied as potential caries preventive agents due to some advantages compared to traditional means of fluoride caries therapy. The aim of the work, which continues the earlier research of ammonium hexafluorosilicates with aromatic amino acid cations, is the synthesis, establishment of physicochemical properties and biological activity of 3-(3-aminophenyl)propionic, 3-(4-aminophenyl)propionic, 2-amino-2- phenylbutyric acid hexafluorosilicates as potential caries preventive agents. 3-(3-Aminophenyl)propionic, 3-(4-aminophenyl)propionic, 2-amino-2-phenylbutyric acid hexafluorosilicates (I–III, respectively) were synthesized in near-quantitative yields by reacting methanolic solutions of the corresponding amino acids with excess 45% silicon hydrofluoric acid. The isolated complexes were identified using the methods of elemental analysis, IR, NMR, 19F and mass spectroscopy. The solubility of I–III in water was established, which is 0.11–0.32 mol. %. The researched compounds I–III and reference drugs – NaF and (NH4)2SiF6 – were introduced into gels based on the Na-salt of carboxymethylcellulose, which were applied to the teeth and gums of rats. In an experiment on an experimental caries model, it was established that the caries preventive efficiency (СPE) of NaF, (NH4)2SiF6, I–III is 30.3%, 44.7%, 23.7%, 38.5%, 26.3%, respectively, that is, only the СPE of compound II exceeds the corresponding indicator for the reference preparation NaF by 1.27 times, while the СPE values of compounds I and III are inferior to both reference preparations. All studied fluoride preparations effectively normalize the biochemical indicators of dental pulp and homogenate of the oral mucosa of rats (phosphatase, elastase, urease and lysozyme activities, malondialdehyde level) that were on a cariogenic diet, and hexafluorosilicates in some cases are more effective compared to NaF.