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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 pulvinic acid; b) the structure of norbadione A; two pulvinic acid motives in the structure of norbadione A are bolded.
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pone.0140602.g001: a) The structure of pulvinic acid; b) the structure of norbadione A; two pulvinic acid motives in the structure of norbadione A are bolded.

Mentions: Le Roux et al. discovered that a pigment norbadione A from the edible mushroom Xerocomus badius is a potent natural antioxidant and is especially interesting due to its capacity to reduce the toxicity of ionizing radiation, since the number of known compounds with this ability is rather limited [3]. Unfortunately the compound was found to be cytotoxic, but still presented a promising lead for the development of less toxic derivatives. The pulvinic acid scaffold, which is an important structural motif of norbadione A (Fig 1), was used as a starting point for the synthesis of 18 related compounds, whose experimental evaluation confirmed their antioxidant activity [4]. Another series 28 pulvinic acid derivatives was experimentally evaluated for their antioxidant capacity, and the obtained data was used for the construction of quantitative structure-activity relationship (QSAR) models, which additionally pointed out coumarines as potential antioxidants [5].


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 pulvinic acid; b) the structure of norbadione A; two pulvinic acid motives in the structure of norbadione A are bolded.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140602.g001: a) The structure of pulvinic acid; b) the structure of norbadione A; two pulvinic acid motives in the structure of norbadione A are bolded.
Mentions: Le Roux et al. discovered that a pigment norbadione A from the edible mushroom Xerocomus badius is a potent natural antioxidant and is especially interesting due to its capacity to reduce the toxicity of ionizing radiation, since the number of known compounds with this ability is rather limited [3]. Unfortunately the compound was found to be cytotoxic, but still presented a promising lead for the development of less toxic derivatives. The pulvinic acid scaffold, which is an important structural motif of norbadione A (Fig 1), was used as a starting point for the synthesis of 18 related compounds, whose experimental evaluation confirmed their antioxidant activity [4]. Another series 28 pulvinic acid derivatives was experimentally evaluated for their antioxidant capacity, and the obtained data was used for the construction of quantitative structure-activity relationship (QSAR) models, which additionally pointed out coumarines as potential antioxidants [5].

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.