ABSTRACT
Tyrosinase inhibitory activity of flavonols, galangin, kaempferol and quercetin, was found to come from their ability to chelate copper in the enzyme. In contrast, the corresponding flavones, chrysin. apigenin and luteolin, did not chelate copper in the enzyme. The chelation mechanism seems to be specific to flavonols as long as the 3-hydroxyl group is free. Interestingly, flavonols affect the enzyme activity in different ways. For example, quercetin behaves as a cofactor and does not inhibit monophenolase activity. On the other hand, galangin inhibits monophenolase activity and does not act as a cofactor. Kaempferol neither acts as a cofactor nor inhibits monophenolase activity. However, these three flavonols are common to inhibit diphenolase activity by chelating copper in the enzyme.
Subject(s)
Flavanones , Flavonoids/pharmacology , Kaempferols , Monophenol Monooxygenase/antagonists & inhibitors , Quercetin/analogs & derivatives , Arnica/chemistry , Binding Sites , Catechol Oxidase/antagonists & inhibitors , Catechol Oxidase/chemistry , Chelating Agents/metabolism , Chelating Agents/pharmacology , Copper/metabolism , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Flavones , Flavonoids/metabolism , Flavonols , Fungal Proteins/antagonists & inhibitors , Fungal Proteins/chemistry , Inhibitory Concentration 50 , Kinetics , Levodopa/metabolism , Monophenol Monooxygenase/chemistry , Oxidation-Reduction , Plant Extracts/chemistry , Plants, Medicinal , Quercetin/metabolism , Quercetin/pharmacology , Spectrophotometry , Structure-Activity RelationshipABSTRACT
Tyrosinase inhibitory and antioxidant activity of gallic acid and its series of alkyl chain esters were investigated. All inhibited the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by mushroom tyrosinase. However, gallic acid and its short alkyl chain esters were oxidized as substrates yielding the colored oxidation products. In contrast, the long alkyl chain esters inhibited the enzyme activity without being oxidized. This indicates that the carbon chain length is associated with their tyrosinase inhibitory activity, presumably by interacting with the hydrophobic protein pocket in the enzyme. On the other hand, the esters, regardless their carbon chain length, showed potent scavenging activity on the autoxidation of linoleic acid and 1,1-diphenyl-2-p-picryhydrazyl (DPPH) radical, suggesting that the alkyl chain length is not related to the activity. The effects of side-chain length of gallates in relation to their antibrowning activity are studied.
Subject(s)
Antioxidants/chemical synthesis , Gallic Acid/analogs & derivatives , Gallic Acid/chemical synthesis , Monophenol Monooxygenase/antagonists & inhibitors , Agaricales/enzymology , Antioxidants/pharmacology , Drug Design , Food Preservation , Gallic Acid/pharmacology , Kinetics , Oxidation-Reduction , Structure-Activity RelationshipABSTRACT
A common flavonol, kaempferol, isolated from the fresh flower petals of Crocus sativus L. (Iridaceae) was found to inhibit the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by mushroom tyrosinase with an ID(50) of 67 microgram/mL (0.23 mM). Interestingly, its 3-O-glycoside derivatives did not inhibit this oxidation. The inhibition kinetics analyzed by a Lineweaver-Burk plot found kaempferol to be a competitive inhibitor, and this inhibitory activity presumably comes from its ability to chelate copper in the enzyme. This copper chelation mechanism can be applicable for all of the flavonols as long as their 3-hydroxyl group is free. However, quercetin, kaempferol, and galangin each affect the oxidation of L-tyrosine in somewhat different ways.
Subject(s)
Flavonoids/chemistry , Kaempferols , Liliaceae , Monophenol Monooxygenase/antagonists & inhibitors , Quercetin/analogs & derivatives , Flavonoids/isolation & purification , Humans , Melanins/antagonists & inhibitors , Plant Extracts/chemistry , Quercetin/chemistry , Quercetin/isolation & purificationABSTRACT
A series of alpha,beta-unsaturated aldehydes, otherwise known as (2E)-alkenals, characterized from the olive Olea europaea L. (Oleaceae) oil flavor was found to inhibit the oxidation of L-3, 4-dihydroxyphenylalanine (L-DOPA) catalyzed by mushroom tyrosinase, and the inhibition kinetics analyzed by a Lineweaver-Burk plot found that they are noncompetitive inhibitors. The inhibition mechanism presumably comes from their ability to form a Schiff base with a primary amino group in the enzyme. In addition, the hydrophobic alkyl chain length from the hydrophilic enal group seems to relate to their affinity to the enzyme, and this results in their inhibitory potency.
Subject(s)
Flavoring Agents/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Plant Oils , Kinetics , Models, Chemical , Olive Oil , Structure-Activity RelationshipABSTRACT
By bioassay-guided fractionation using mushroom tyrosinase (EC 1.14.18.1), 2-hydroxy-4-methoxybenzaldehyde was characterized as the principal tyrosinase inhibitor from three East African medicinal plants, the root of Mondia whitei (Hook) Skeels (Asclepiaceae), the root of Rhus vulgaris Meikle (Anacardiaceae), and the bark of Sclerocarya caffra Sond (Anacardiaceae). It inhibited the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) by mushroom tyrosinase with an ID50 of 4.3 micrograms/ml (0.03 mM). The inhibition kinetics analyzed by a Lineweaver-Burk plot found this simple benzaldehyde derivative to be a mixed type inhibitor for this oxidation and affects on the enzyme in several ways. Based on finding this potent tyrosinase inhibitor, various related analogues were also tested in order to gain new insights into their inhibitory functions on a molecular basis.
Subject(s)
Benzaldehydes/pharmacology , Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Plants, Medicinal/chemistry , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Benzaldehydes/isolation & purification , Drug Screening Assays, Antitumor , Enzyme Inhibitors/isolation & purification , Humans , Kinetics , Melanoma/pathology , Mice , Tumor Cells, CulturedABSTRACT
Bioassay-guided fractionation monitored by mushroom tyrosinase (EC 1.14.18.1) activity, afforded six inhibitors from three Bolivian medicinal plants, Buddleia coriacea, Gnaphalium cheiranthifolium, and Scheelea princeps. These inhibitors, which are all known phenolic compounds, inhibited the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) mediated by a mushroom tyrosinase.
Subject(s)
Monophenol Monooxygenase/antagonists & inhibitors , Plants, Medicinal/chemistry , Basidiomycota/enzymology , BoliviaABSTRACT
Anacardic acids, 2-methylcardols, and cardols isolated from various parts of the cashew [Anacardium occidentale] (Anacardiaceae) fruit have been found to exhibit tyrosinase inhibitory activity. Kinetic studies with the two principal active compounds, 6-[8(Z),11(Z),14-pentadecatrienyl]salicylic acid and 5-[8(Z),11(Z),14-pentadecatrienyl]resorcinol, have indicated that both of these phenolic compounds exhibit characteristic competitive inhibition of the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) by mushroom tyrosinase.
