Dopamine release and molecular modeling study of some coumarin derivatives

4-aryl-2-amino-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-3-carbonitrile (1), 4-aryl-2-oxo-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-3-carbonitriles (2a–2c), 3-(6-aryl-1,2,5,6- tetrahydro-2-thioxopyrimidin-4-yl)-4-hydroxy-2H-chromen-2-one (3a, 3b) and pyrazol-3-yl-4-hydroxycoumarin derivatives (4a–4c, 5, 6a, 6b, 7a, 7b, and 8a–8c) were prepared in order to measure their % change dopamine release in comparison to amphetamine as reference, using PC-12 cells in different concentrations. In addition, the molecular modeling study of the compounds into 3BHH receptor was also demonstrated. The calculated inhibition constant (ki) implemented in the AutoDock program revealed identical correlation with the experimental results to that obtained binding free energy (ΔGb) as both parameters revealed reasonable correlation coefficients (R2) being 0.51 involving 10 compounds; (1, 2b, 2c, 3a, 3b, 4a, 4b, 6a, and 8c).

Graphical abstractThis work is concerning the study of dopamine release for some 3-aryl substituted-4-hydroxycoumarin derivatives in PC-12 cells using Amphetamine as reference standard and the study of their molecular modeling into 3BHH receptor was also demonstrated.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Dopamine release of some 3-substituted-4-hydroxycoumarin derivatives was studied. ► Molecular modeling study of the compounds into 3BHH receptor was also demonstrated. ► Aminopyridin-3-carbonitrile derivatives gave the highest fractional DA release. ► Pyrazole compounds showed best docking result with correlated DA releasing effects.