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In Silico Discovery of Novel Potent Antioxidants on the Basis of Pulvinic Acid and Coumarine Derivatives and Their Experimental Evaluation.

Martinčič R, Mravljak J, Švajger U, Perdih A, Anderluh M, Novič M - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemometrics, National Institute of Chemistry Slovenia, Hajdrihova 19, 1000, Ljubljana, Slovenia.

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.

No MeSH data available.


a) The structure of tetronic acid; b) the vinylogous acid fragment (bolded), common to the pulvinic acid and coumarine derivatives.
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pone.0140602.g010: a) The structure of tetronic acid; b) the vinylogous acid fragment (bolded), common to the pulvinic acid and coumarine derivatives.

Mentions: First, the eMolecules database was screened for derivatives of tetronic acid (Fig 10), which is five-membered ring fragment of the pulvinic acid containing a vinylogous acid fragment, presumed to be the bearer of the antioxidant activity of such compounds [5]. Only 29 hits were obtained when screening for compounds containing the tetronic acid fragment; since we were not satisfied with the number of obtained hits, the search was broadened to all compounds containing the vinylogous acid fragment (Fig 10). About 4.000 hits were obtained in this manner, which were further refined. Since the substructure search for the vinylogous acid fragment resulted in structurally very diverse hits, the main emphasis in the first step of the refinement was put on the similarity of selected compounds with the reference compounds used for the QSAR models development [6], while in the second step some compounds were removed due to their potentially problematic structural features (such as epoxides, azo compounds, etc.) Finally, a pool of 239 compounds was selected (provided in the Supporting Information as S1 File).


In Silico Discovery of Novel Potent Antioxidants on the Basis of Pulvinic Acid and Coumarine Derivatives and Their Experimental Evaluation.

Martinčič R, Mravljak J, Švajger U, Perdih A, Anderluh M, Novič M - PLoS ONE (2015)

a) The structure of tetronic acid; b) the vinylogous acid fragment (bolded), common to the pulvinic acid and coumarine derivatives.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608598&req=5

pone.0140602.g010: a) The structure of tetronic acid; b) the vinylogous acid fragment (bolded), common to the pulvinic acid and coumarine derivatives.
Mentions: First, the eMolecules database was screened for derivatives of tetronic acid (Fig 10), which is five-membered ring fragment of the pulvinic acid containing a vinylogous acid fragment, presumed to be the bearer of the antioxidant activity of such compounds [5]. Only 29 hits were obtained when screening for compounds containing the tetronic acid fragment; since we were not satisfied with the number of obtained hits, the search was broadened to all compounds containing the vinylogous acid fragment (Fig 10). About 4.000 hits were obtained in this manner, which were further refined. Since the substructure search for the vinylogous acid fragment resulted in structurally very diverse hits, the main emphasis in the first step of the refinement was put on the similarity of selected compounds with the reference compounds used for the QSAR models development [6], while in the second step some compounds were removed due to their potentially problematic structural features (such as epoxides, azo compounds, etc.) Finally, a pool of 239 compounds was selected (provided in the Supporting Information as S1 File).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemometrics, National Institute of Chemistry Slovenia, Hajdrihova 19, 1000, Ljubljana, Slovenia.

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.

No MeSH data available.