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.


Histogram of the calculated k’ values in the BCB assay.Rate constants of quercetin, resveratrol and Trolox are not depicted due to being much higher. GA–gallic acid.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140602.g009: Histogram of the calculated k’ values in the BCB assay.Rate constants of quercetin, resveratrol and Trolox are not depicted due to being much higher. GA–gallic acid.

Mentions: An attempt was made to evaluate also the kinetics of the reactions of LOO• with the tested compounds. Since the principles behind BCB assay and the 2-DR assay are quite similar (in both cases, an in situ source of radicals attacks the probe, that should be protected by the evaluated compound, we decided to use the same procedure as for the calculation of rate constants in the 2-DR assay [47]. By plotting the values of 1/∆A (where ∆A represents the difference between the initial and the final absorbance) versus the antioxidant concentration, linear plots were obtained, and the rate constants can be obtained from the slopes by the following equation:k=slope×kβC×[βC]×A0(2)where kβC represents the rate constant of the reaction of β-carotene with LOO•, [βC] is the concentration of β-carotene and A0 stands for the control absorbance. However, since we found no literature data on value of kβC, the exact rate constants could not be calculated. However, given that the values of kβC and [βC] are constant, the kinetic behavior of the tested compounds can still be compared just from the product of the slope and A0, which we named k’. The calculated k’ values are presented in Table 5 and graphically depicted in Fig 9.


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 calculated k’ values in the BCB assay.Rate constants of quercetin, resveratrol and Trolox are not depicted due to being much higher. GA–gallic acid.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140602.g009: Histogram of the calculated k’ values in the BCB assay.Rate constants of quercetin, resveratrol and Trolox are not depicted due to being much higher. GA–gallic acid.
Mentions: An attempt was made to evaluate also the kinetics of the reactions of LOO• with the tested compounds. Since the principles behind BCB assay and the 2-DR assay are quite similar (in both cases, an in situ source of radicals attacks the probe, that should be protected by the evaluated compound, we decided to use the same procedure as for the calculation of rate constants in the 2-DR assay [47]. By plotting the values of 1/∆A (where ∆A represents the difference between the initial and the final absorbance) versus the antioxidant concentration, linear plots were obtained, and the rate constants can be obtained from the slopes by the following equation:k=slope×kβC×[βC]×A0(2)where kβC represents the rate constant of the reaction of β-carotene with LOO•, [βC] is the concentration of β-carotene and A0 stands for the control absorbance. However, since we found no literature data on value of kβC, the exact rate constants could not be calculated. However, given that the values of kβC and [βC] are constant, the kinetic behavior of the tested compounds can still be compared just from the product of the slope and A0, which we named k’. The calculated k’ values are presented in Table 5 and graphically depicted in Fig 9.

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.