Synthesis of novel β-amino carbonyl derivatives and their inhibition effects on some metabolic enzymes

Abstract

In this study, we reported the synthesis, characterization and activity-structure relationship of novel β-amino carbonyl compounds. Some novel bis-β-amino carbonyl (4a-e) and mono-β-amino carbonyl (5a-e) compounds were synthesized by using CeCl3·7H2O catalyzed Mannich-type reaction. The title compounds were characterized by FTIR, elemental analysis, 13C NMR and 1H NMR techniques. In addition, the crystal and molecular structures of 5a, 5d and 5e were illuminated by single crystal X-ray diffraction. The activity-structure relationship was established by analyzing the enzyme activity of synthesized β-amino carbonyl compounds, which were effectively inhibited by human carbonic anhydrase I (hCA I), and II (hCA II) isoenzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). According to the activity-structure relationship, the Ki values of the β-amino carbonyl compounds were determined between 11.42 and 70.71 nM on hCA I, 28.66–77.59 nM on hCA II, 18.66–95.35 nM on AChE and 9.54–94.70 nM on BChE. We hope that these compounds may have promising new potentials in both CA isoenzymes AChE and BChE enzyme inhibitors.