NMR and DFT studies for the tautomeric characterization of a novel quinoxalinone derivative; In silico testing against monoamine oxidases
Vasiliki Paschou1, Filippos Panteleimon Chatzipieris1, Demeter Tzeli2, Stella Manta3, Thomas Mavromoustakos1,*
1 Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece
2 Laboratory of Physical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece
3 Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
* Correspondence author: tmavrom@chem.uoa.gr
DOI: 10.62579/JAGC0020
Abstract
Quinoxalinones are extensively studied in medicinal chemistry, serving as promising pharmacophores with broad biological activity. More specifically, researchers focus on exploring their activity as central nervous system (CNS) agents. An interesting phenomenon that concerns many researchers is that various quinoxalinone analogues are characterized by imine-enamine tautomerism. However, there is limited research on how each tautomeric form acts on a certain biological target. This study investigates the tautomerism of a novel quinoxalinone derivative in conjunction with the in silico investigation of its inhibitory effect against monoamine oxidases (MAOs). NMR spectroscopy as well as theoretical DFT calculations were employed to examine the tautomeric equilibrium. A plausible transition state geometry based on DFT computational studies is proposed as well. Additionally, molecular docking simulations and MM/GBSA calculations were carried out to test the inhibition efficacy of the synthesized compound on the MAO enzymes.
Key words
Quinoxalinones, imine-enamine tautomerism, NMR spectroscopy, DFT calculations, transition state, Molecular Docking studies, MM/GBSA, Monoamine oxidase B, Monoamine oxidase A, MAO-B, MAO-A
NMR and DFT studies for the tautomeric characterization of a novel quinoxalinone derivative