and Characterization of Kurarinone as a Dopamine D Receptor Antagonist and D and D Receptor Agonist.

Alterations in the expression and/or activity of brain G-protein-coupled receptors (GPCRs) such as dopamine DR, DR, DR, and DR, vasopressin VR, and serotonin 5-HTR are noted in various neurodegenerative diseases (NDDs). Since studies have indicated that flavonoids can target brain GPCRs and provide neuroprotection via inhibition of monoamine oxidases (hMAOs), our study explored the functional role of kurarinone, an abundant lavandulated flavonoid in , on dopamine receptor subtypes, VR, 5-HTR, and hMAOs. Radioligand binding assays revealed considerable binding of kurarinone on DR, DR, and DR. Functional GPCR assays unfolded the compound's antagonist behavior on DR (IC 42.1 ± 0.35 μM) and agonist effect on DR and DR (EC 22.4 ± 3.46 and 71.3 ± 4.94 μM, respectively). Kurarinone was found to inhibit hMAO isoenzymes in a modest and nonspecific manner. Molecular docking displayed low binding energies during the intermolecular interactions of kurarinone with the key residues of the deep orthosteric binding pocket and the extracellular loops of DR, DR, and DR, validating substantial binding affinities to these prime targets. With appreciable DR and DR agonism and DR antagonism, kurarinone might be a potential compound that can alleviate clinical symptoms of Parkinson's disease and other NDDs.