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

Bicer A., Kaya R., Yakali G., GÜLTEKİN M. S., TURGUT CİN G., GÜLÇİN İ.

JOURNAL OF MOLECULAR STRUCTURE, vol.1204, 2020 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1204
  • Publication Date: 2020
  • Doi Number: 10.1016/j.molstruc.2019.127453
  • Journal Name: JOURNAL OF MOLECULAR STRUCTURE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chimica, Compendex, INSPEC
  • Keywords: Mannich-type reactions, Multi-component reaction, beta-amino carbonyl compound, Carbonic anhydrase, Cholinesterase, Crystal structure, ERYTHROCYTE ISOZYMES I, MANNICH-TYPE REACTIONS, CRYSTAL-STRUCTURE, SULFONAMIDE DERIVATIVES, ANHYDRASE INHIBITION, 1ST SYNTHESIS, ONE-POT, ACETYLCHOLINESTERASE, BUTYRYLCHOLINESTERASE, ANTIOXIDANT
  • Akdeniz University Affiliated: Yes

Abstract

In this study, we reported the synthesis, characterization and activity-structure relationship of novel beta-amino carbonyl compounds. Some novel bis-beta-amino carbonyl (4a-e) and mono-beta-amino carbonyl (5a-e) compounds were synthesized by using CeCl3 center dot 7H(2)O catalyzed Mannich-type reaction. The title compounds were characterized by FTIR, elemental analysis, C-13 NMR and H-1 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 beta-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 K-i values of the beta-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. (C) 2019 Elsevier B.V. All rights reserved.