Synthesis, characterization, and biological studies of chalcone derivatives containing Schiff bases: Synthetic derivatives for the treatment of epilepsy and Alzheimer's disease.

Abstract

In this study, first, Schiff base-containing chalcone derivatives were synthesized. The human carbonic anhydrase (hCA) isoenzymes I and II were then purified from human erythrocytes using Sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography. In addition, the inhibitory effects of the newly synthesized compounds on the activities of hCA and acetylcholinesterase (AChE) were investigated in vitro, using the esterase and acetylcholine iodide method. The IC50 values were determined and the Ki values of AChE and hCA activities were calculated from the Lineweaver-Burk graphs determined in this study. The hCA I isoform was inhibited by these chalcone derivatives containing Schiff bases (3a-j and 5a-f) in low nanomolar levels, whose Ki values ranged between 141.88 ± 24.10 and 2,234.47 ± 38.11 nM. Against the physiologically dominant isoform hCA II, the compounds demonstrated Ki values varying from 199.31 ± 40.45 to 602.79 ± 263.22 nM. Also, these compounds effectively inhibited AChE, with Ki values ranging from 20.41 ± 6.04 to 125.94 ± 23.88 nM. According to these results, the newly synthesized molecules were found to be potent inhibitors of these enzymes.

• Authors: Ümit M Koçyiğit, Hayreddin Gezegen, Parham Taslimi
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 353 Issue 12 Pg. e2000202 (Dec 2020) ISSN: 1521-4184 [Electronic] Germany
• PMID: 32815568 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2020 Deutsche Pharmazeutische Gesellschaft.

Chemical References

• Anticonvulsants
• Carbonic Anhydrase Inhibitors
• Chalcones
• Cholinesterase Inhibitors
• GPI-Linked Proteins
• Schiff Bases
• ACHE protein, human
• Acetylcholinesterase
• Carbonic Anhydrase I
• Carbonic Anhydrase II
• CA1 carbonic anhydrase, human
• CA2 protein, human

Topics

• Acetylcholinesterase (metabolism)
• Alzheimer Disease (drug therapy, enzymology, psychology)
• Anticonvulsants (chemical synthesis, pharmacology)
• Carbonic Anhydrase I (antagonists & inhibitors, metabolism)
• Carbonic Anhydrase II (antagonists & inhibitors, metabolism)
• Carbonic Anhydrase Inhibitors (chemical synthesis, pharmacology)
• Chalcones (chemical synthesis, pharmacology)
• Cholinesterase Inhibitors (chemical synthesis, pharmacology)
• Drug Design
• Erythrocytes (enzymology)
• GPI-Linked Proteins (antagonists & inhibitors, metabolism)
• Molecular Structure
• Schiff Bases
• Structure-Activity Relationship