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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.


Histogram of the experimentally determined IC50 values in the 2-DR assay.TR–Trolox; AE–aesculin.
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pone.0140602.g007: Histogram of the experimentally determined IC50 values in the 2-DR assay.TR–Trolox; AE–aesculin.

Mentions: Most of the compounds that were active in the DPPH assay were also displayed activity in the 2-DR assay, with the exception of compound 10, that could not be evaluated due to its low water solubility, and compound 19, which was found to have a pro-oxidant effect in the 2-DR assay system. The reason could be that the compound 19 is able to recycle Fe3+ back to Fe2+, thus promoting the Fenton reaction [50]. The pro-oxidant effect was also observed with some of the standard antioxidants, more precisely gallic acid, resveratrol, curcumin and quercetin. The spectrum of activities was a bit wider than in the case of the DPPH assay, with the IC50 values ranging from approximately 10 to 100 μM (Table 3 and Fig 7). Novel compounds clearly outperformed the standard antioxidants Trolox and aesculin regarding the antioxidant activity. The determined IC50 values of aesculin and Trolox correspond well with the published literature data, giving us confidence in the accuracy of our measurements.


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)

Histogram of the experimentally determined IC50 values in the 2-DR assay.TR–Trolox; AE–aesculin.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140602.g007: Histogram of the experimentally determined IC50 values in the 2-DR assay.TR–Trolox; AE–aesculin.
Mentions: Most of the compounds that were active in the DPPH assay were also displayed activity in the 2-DR assay, with the exception of compound 10, that could not be evaluated due to its low water solubility, and compound 19, which was found to have a pro-oxidant effect in the 2-DR assay system. The reason could be that the compound 19 is able to recycle Fe3+ back to Fe2+, thus promoting the Fenton reaction [50]. The pro-oxidant effect was also observed with some of the standard antioxidants, more precisely gallic acid, resveratrol, curcumin and quercetin. The spectrum of activities was a bit wider than in the case of the DPPH assay, with the IC50 values ranging from approximately 10 to 100 μM (Table 3 and Fig 7). Novel compounds clearly outperformed the standard antioxidants Trolox and aesculin regarding the antioxidant activity. The determined IC50 values of aesculin and Trolox correspond well with the published literature data, giving us confidence in the accuracy of our measurements.

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.