Screening for cyclooxygenase 2 inhibitors from natural compounds of Radix Glycyrrhizae using computer simulation

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Screening for cyclooxygenase 2 inhibitors from natural compounds of Radix Glycyrrhizae using computer simulation

Journal Title: Traditional Medicine Research - Year 2018, Vol 3, Issue 3

Abstract

Objective: To explore the molecular basis of the effects of Gancao (Radix Glycyrrhizae, GC) on inflammation through the inhibition of cyclooxygenase 2 (COX-2). Methods: The Discovery Studio 4.5 System was used to predict the physicochemical properties of GC molecular compounds. The Ligand Profiler was used to screen for natural GC components that could combine with the COX-2 pharmacophores. The AutoDock Vina 1.1.2 software was used for the molecular docking of the natural GC components with the COX-2 protein. Results: The aromatics were the closest to the non-steroidal anti-inflammatory drugs in terms of the three properties, namely molecular weight, molecular surface area, and molecular solubility, followed by the flavonoids; whereas the terpenoids/saponins differed most from the non-steroidal anti-inflammatory drugs in terms of the three properties; and the aliphatics were inconsistent. One hundred and eighteen small molecules were obtained through the pharmacophore screening using GC. The molecular binding energy (MBE) results demonstrated that the MBE value of the flavonoids/aromatics, obtained from their binding with the COX-2 protein, was lower than that obtained from their binding with the substrate, metabolism of arachidonic acid, whereas the MBE value of the aliphatics/terpenoids, obtained from their binding with the COX-2 protein, was higher than that obtained from their binding with the substrate, arachidonic acid. Finally, further filtration, based on the physicochemical properties and the molecular binding energies of the small molecules, was carried out. Forty-two natural GC components, including 35 flavonoid and 7 aromatic constituents, with low binding energies and potential inhibitory effects on COX-2, were screened. Conclusion: Using the three-step program, pharmacophore screening, molecular docking, and physicochemical properties analysis, we screened out 35 flavonoid molecules and 7 aromatic molecules, which may be potential COX-2 inhibitors, from GC. Two of the 35 flavonoid molecules (licochalcone A and glabridin) have been confirmed in the laboratory to have inhibitory effects on COX-2. Our findings provide a material basis for the development of non-steroidal GC drugs.

Authors and Affiliations

Ming Yang, Yi Jin, Li-Ping Yang

Keywords

Radix Glycyrrhizae|COX-2|Pharmacophores|Molecular docking|Physicochemical properties

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EP ID EP45230
DOI 10.12032/TMR201811070
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