Limits...
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.


Four active pulvinic acid derivatives (IDs: 11, 15, 36, 49 [6]), selected for the construction of the pharmacophore model.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4608598&req=5

pone.0140602.g011: Four active pulvinic acid derivatives (IDs: 11, 15, 36, 49 [6]), selected for the construction of the pharmacophore model.

Mentions: A ligand-based pharmacophore model was derived using LigandScout software [71], on the basis of four selected active pulvinic acid derivatives (IDs: 11, 15, 36, 49 [6]) (Fig 11). Several unique conformations were first calculated for each structure by applying LigandScout conformer generator coupled to the OMEGA software [72] with the following settings: maximum number of output conformers per molecule = 25; RMS threshold to duplicate conformers = 0.8 Å; maximum number of generated conformers per molecule = 30000; maximum number of intermediate conformers per molecule = 4000; maximum search time = 30 seconds; energy window = 10 kcal/mol. The generated conformers were dynamically aligned, and 10 merged feature pharmacophore models were produced. These were assessed using a scoring function combining the pharmacophore fit and the atom shape overlay, and the model with the highest score of 0.9010 was selected for further use.


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)

Four active pulvinic acid derivatives (IDs: 11, 15, 36, 49 [6]), selected for the construction of the pharmacophore model.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140602.g011: Four active pulvinic acid derivatives (IDs: 11, 15, 36, 49 [6]), selected for the construction of the pharmacophore model.
Mentions: A ligand-based pharmacophore model was derived using LigandScout software [71], on the basis of four selected active pulvinic acid derivatives (IDs: 11, 15, 36, 49 [6]) (Fig 11). Several unique conformations were first calculated for each structure by applying LigandScout conformer generator coupled to the OMEGA software [72] with the following settings: maximum number of output conformers per molecule = 25; RMS threshold to duplicate conformers = 0.8 Å; maximum number of generated conformers per molecule = 30000; maximum number of intermediate conformers per molecule = 4000; maximum search time = 30 seconds; energy window = 10 kcal/mol. The generated conformers were dynamically aligned, and 10 merged feature pharmacophore models were produced. These were assessed using a scoring function combining the pharmacophore fit and the atom shape overlay, and the model with the highest score of 0.9010 was selected for further use.

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.