top of page

GPCR News 

Post: Blog2_Post

In Vitro and In Silico Characterization of Kurarinone as a Dopamine D 1A Receptor Antagonist and ...

Alterations in the expression and/or activity of brain G-protein-coupled receptors (GPCRs) such as dopamine D1R, D2LR, D3R, and D4R, vasopressin V1AR, and serotonin 5-HT1AR 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 Sophora flavescens, on dopamine receptor subtypes, V1AR, 5-HT1AR, and hMAOs. Radioligand binding assays revealed considerable binding of kurarinone on D1R, D2LR, and D4R. Functional GPCR assays unfolded the compound's antagonist behavior on D1R (IC50 42.1 ± 0.35 μM) and agonist effect on D2LR and D4R (EC50 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 D1R, D2LR, and D4R, validating substantial binding affinities to these prime targets. With appreciable D2LR and D4R agonism and D1R antagonism, kurarinone might be a potential compound that can alleviate clinical symptoms of Parkinson's disease and other NDDs.

1 view0 comments

Recent Posts

See All