Structure–Activity relationship studies of two dietary flavonoids and their Nitric Oxide Synthase inhibition activity by spectroscopic and quantum/classical computational techniques

The Nitric Oxide Synthase inhibitory activity of two dietary phytocompounds naringenin and quercetin that belong to the family of flavonoids was studied by spectroscopic and computational methods. The determining role played by the global reactivity parameters that were calculated using spectroscopic and computational methods were correlated with the Nitric Oxide Synthase inhibitory activity by a Quantitative Structure–Activity Relationship (QSAR) study. The inter and intramolecular charge–transfer interactions responsible for the biological activity of naringenin and quercetin were studied using Natural Bond Orbital Analysis. The reactive sites of the title compounds were studied using their molecular electrostatic map. The likelihood of naringenin and quercetin to be a small drug molecule was determined by Lipinski’s rule. The molecular dynamics and docking studies were carried out to test the energetic and structural favorability of the inhibition of Nitric Oxide Synthase by small drug molecules naringenin and quercetin. Experimental cell culture-based in vitro assays were done to test theoretical predictions. A QSAR study revealed that for Nitric Oxide Synthase inhibitory activity to be better, the compounds belonging to the family of flavonoids ought to have a more negative ionization energy and chemical softness while bandgap and electrophilicity index ought to be more positive.