title: In Silico Discovery of Novel Potent Antioxidants on the Basis of Pulvinic Acid and Coumarine Derivatives and Their Experimental Evaluation.
abstract: A pigment from the edible mushroom Xerocomus badius norbadione A, which is a natural derivative of pulvinic acid, was found to possess antioxidant properties. Since the pulvinic acid represents a novel antioxidant scaffold, several other derivatives were recently synthetized and evaluated experimentally, along with some structurally related coumarine derivatives. The obtained data formed the basis for the construction of several quantitative structure-activity and pharmacophore models, which were employed in the virtual screening experiments of compound libraries and for the prediction of their antioxidant activity, with the goal of discovering novel compounds possessing antioxidant properties. A final prioritization list of 21 novel compounds alongside 8 established antioxidant compounds was created for their experimental evaluation, consisting of the DPPH assay, 2-deoxyribose assay, β-carotene bleaching assay and the cellular antioxidant activity assay. Ten novel compounds from the tetronic acid and barbituric acid chemical classes displayed promising antioxidant activity in at least one of the used assays, that is comparable to or even better than some standard antioxidants. Compounds 5, 7 and 9 displayed good activity in all the assays, and were furthermore effective preventers of oxidative stress in human peripheral blood mononuclear cells, which are promising features for the potential therapeutic use of such compounds.
authors.affiliation: Laboratory of Chemometrics, National Institute of Chemistry Slovenia, Hajdrihova 19, 1000, Ljubljana, Slovenia.
authors.forename: Rok
authors.initials: R
authors.lastname: Martinčič
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000, Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Mravljak
authors.affiliation: Blood transfusion centre of Slovenia, Šlajmerjeva 6, 1000, Ljubljana, Slovenia.
authors.forename: Urban
authors.initials: U
authors.lastname: Švajger
authors.affiliation: Laboratory for Biocomputing and Bioinformatics, National Institute of Chemistry Slovenia, Hajdrihova 19, 1000, Ljubljana, Slovenia.
authors.forename: Andrej
authors.initials: A
authors.lastname: Perdih
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000, Ljubljana, Slovenia.
authors.forename: Marko
authors.initials: M
authors.lastname: Anderluh
authors.affiliation: Laboratory of Chemometrics, National Institute of Chemistry Slovenia, Hajdrihova 19, 1000, Ljubljana, Slovenia.
authors.forename: Marjana
authors.initials: M
authors.lastname: Novič
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology*; D003198:Computer Simulation; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D010851:Picrates / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D019207:beta Carotene / Q000737:chemistry
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D002264:Carboxylic Acids; D003374:Coumarins; D007783:Lactones; D010851:Picrates; D054852:Small Molecule Libraries; D019207:beta Carotene; C004931:1,1-diphenyl-2-picrylhydrazyl; C492654:pulvinic acid