title: Identification of Novel Nitrosative Stress Inhibitors through Virtual Screening and Experimental Evaluation.
abstract: Nitrosative and oxidative stress, associated with the generation of excessive reactive nitrogen and oxygen radical species respectively, are thought to contribute to protein misfolding diseases which represent a group of neurodegenerative disorders that are characterized by protein aggregation and plaque formation. Curcumin, a polyphenolic compound, possesses diverse anti-inflammatory, antitumor, and antioxidant properties. Several studies have revealed that curcumin can reduce the oxidative/nitrosative stress and thereby decrease the neuronal attrition. However, curcumin has poor bioavailability and has raised several concerns focused on its limited clinical impact. The aim of this study was to find other compounds which can assist in decreasing nitrosative stress and possess enhanced bioavailability. Here, use of β-lactoglobulin was examined as a vehicle to transport molecules to the gut. The Zinc database was searched using curcumin as reference and 6457 compounds were selected for the study. These compounds were docked to β-lactoglobulin using Glide to find the best fit ligands. Our studies identified four compounds that bind to β-lactoglobulin and scavenge NOx (free radicals) efficiently.
authors.affiliation: Department of Chemistry & Biochemistry, Northern Arizona University, P. O. Box 5698, Flagstaff, Arizona 86011-5698, USA. suman.sirimulla@nau.edu, mnarayan@utep.edu.|Department of Chemistry, University of Texas at El Paso, 500 W University Ave, El Paso, Texas, 79968, USA. suman.sirimulla@nau.edu, mnarayan@utep.edu.
authors.forename: Suman
authors.initials: S
authors.lastname: Sirimulla
authors.affiliation: Department of Chemistry, University of Texas at El Paso, 500 W University Ave, El Paso, Texas, 79968, USA.
authors.forename: Rituraj
authors.initials: R
authors.lastname: Pal
authors.affiliation: Interdisciplinary Health Sciences, University of Texas at El Paso, 500 W University Ave, El Paso, Texas, 79968, USA.
authors.forename: Mrudula
authors.initials: M
authors.lastname: Raparla
authors.affiliation: Department of Chemistry & Biochemistry, Northern Arizona University, P. O. Box 5698, Flagstaff, Arizona 86011-5698, USA.
authors.forename: Jake B
authors.initials: JB
authors.lastname: Bailey
authors.affiliation: Department of Chemistry, University of Texas at El Paso, 500 W University Ave, El Paso, Texas, 79968, USA.
authors.forename: Rene
authors.initials: R
authors.lastname: Duran
authors.affiliation: Department of Chemistry & Biochemistry, Northern Arizona University, P. O. Box 5698, Flagstaff, Arizona 86011-5698, USA.
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Altamirano
authors.affiliation: Department of Chemistry, University of Texas at El Paso, 500 W University Ave, El Paso, Texas, 79968, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Herndon
authors.affiliation: Department of Chemistry, University of Texas at El Paso, 500 W University Ave, El Paso, Texas, 79968, USA.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Narayan
keywords: Molecular docking; Nitrosative stress; Nitrosative stress inhibitors; Virtual screening; β-Lactoglobulin (β-Lg)