Adenosine deaminase - A target for new piperazine derivatives.

Abstract

The level of adenosine deaminase (ADA) activity increases in pathological effusions. Therefore, the concentration of its substrate, anti-inflammatory adenosine, decreases, thereby aggravating inflammation. Hence, the quest for ADA inhibiting compounds is an actual problem in medicine and pharmacology. This work describes the inhibition of bovine ADA by new synthesized piperazine compounds. 15 compounds were screened; IC50 values for 5 more potent ones of them were between 3.4 and 98.6 μg/ml. The inhibition of activity of intracellular and ecto- forms of ADA by the most effective "compound 1" was of competitive nature. For these two forms of enzyme, the inhibition constants, Ki (1.5 and 115 μM) and IC50 values (6.5 and 480 μM), respectively, differed by nearly two orders. The constant of bimolecular interaction KSV between "compound 1" and the tryptophan residues in ADA was estimated in fluorescence quenching study as of 0.145 ± 0.027 μM. Finally, the molecular interactions between "compound 1" and the bovine enzyme ADA were highlighted through molecular docking studies.

• Authors: Anahit Bakaryan, Luiza Karapetyan, Naira Hakobyan, Emidio Camaioni, Sona Mardanyan, Alvard Antonyan
• Journal: Biophysical chemistry (Biophys Chem) Vol. 277 Pg. 106658 (10 2021) ISSN: 1873-4200 [Electronic] Netherlands
• PMID: 34333397 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Adenosine Deaminase Inhibitors
• Adenosine Deaminase

Topics

• Adenosine Deaminase
• Adenosine Deaminase Inhibitors
• Animals
• Cattle
• Molecular Docking Simulation