Spectroscopic and quantum/classical mechanics based computational studies to compare the ability of Andrographolide and its derivative to inhibit Nitric Oxide Synthase

The inhibition of the enzyme Nitric Oxide Synthase by a bioactive compounds results in it possessing anti-inflammatory property. The ability of Andrographolide and its derivative Isoandrographolide to inhibit Nitric Oxide Synthase was studied using computational and experimental techniques. A combination of UV Spectroscopic and DFT computational techniques were used to calculate the molecular descriptors of the title compounds which were used to establish relationship with its biological activity. The drug-likeness of the compounds was estimated using Lipinski's rule. Molecular dynamics and docking studies were carried out to test for the structural and energetic favourability of the title compounds(ligand) being bound to Nitric Oxide Synthase( Protein) to induce inhibition. The force constant data obtained from IR spectroscopy was used in aid to parametrize force fields used in molecular dynamics simulation. The DFT method was used to perform NBO analysis that revealed the charge transfer interactions responsible for its biological properties. The Molecular Electrostatic Potential (MEP) plot revealed the regions of electrophilic and nucleophilic reactivity of the title compounds. MTT (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay was carried out which revealed the cytotoxicity at different concentrations of the title compounds by which means the biologically safe concentration was determined and therefore at this biologically safe concentration the ability of the compounds to inhibit Nitric Oxide formation was determined. Quantitative Structure-Activity Studies (QSAR) were used to furnish relationship between molecular descriptors and the Nitric Oxide Synthase inhibition activity resulting in anti-inflammatory property, based on the chosen molecular descriptors suggestions were made for the search of more potent Nitric Oxide Synthase inhibitors in the Andrographolide derivative family of compounds. (c) 2019 Elsevier B.V. All rights reserved.