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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 EC50 values in the DPPH assay.AA–ascorbic acid; GA–gallic acid; QU–quercetin; TR–Trolox; CU–curcumin; RE–resveratrol. The EC50 values of scopoletin and aesculin are not depicted, due to being much larger.
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pone.0140602.g005: Histogram of the experimentally determined EC50 values in the DPPH assay.AA–ascorbic acid; GA–gallic acid; QU–quercetin; TR–Trolox; CU–curcumin; RE–resveratrol. The EC50 values of scopoletin and aesculin are not depicted, due to being much larger.

Mentions: The EC50 values of the novel compounds do not differ much (all are in the range of 10–35 μM), and are comparable to the EC50 values of ascorbic acid, Trolox, curcumin and resveratrol, and much higher than the EC50 values of aesculin and scopoletin (Fig 5). However, it should be noted that only compound 19 was able to reach the steady state within one hour, while all other novel compounds required a 24 hour incubation period for the reaction to fully take place. On the other hand, several standard antioxidants (aesculin, scopoletin, curcumin and resveratrol) also required 24 hours of incubation to reach the steady state of the reduced DPPH.


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 EC50 values in the DPPH assay.AA–ascorbic acid; GA–gallic acid; QU–quercetin; TR–Trolox; CU–curcumin; RE–resveratrol. The EC50 values of scopoletin and aesculin are not depicted, due to being much larger.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140602.g005: Histogram of the experimentally determined EC50 values in the DPPH assay.AA–ascorbic acid; GA–gallic acid; QU–quercetin; TR–Trolox; CU–curcumin; RE–resveratrol. The EC50 values of scopoletin and aesculin are not depicted, due to being much larger.
Mentions: The EC50 values of the novel compounds do not differ much (all are in the range of 10–35 μM), and are comparable to the EC50 values of ascorbic acid, Trolox, curcumin and resveratrol, and much higher than the EC50 values of aesculin and scopoletin (Fig 5). However, it should be noted that only compound 19 was able to reach the steady state within one hour, while all other novel compounds required a 24 hour incubation period for the reaction to fully take place. On the other hand, several standard antioxidants (aesculin, scopoletin, curcumin and resveratrol) also required 24 hours of incubation to reach the steady state of the reduced DPPH.

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.