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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.

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.

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.

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.

Cuminaldehyde (p-isopropylbenzaldehyde) was identified as a potent mushroom tyrosinase inhibitor from cumin, a common food spice. This benzaldehyde derivative was found to inhibit the oxidation of l-3,4-dihydroxyphenylalanine (l-DOPA) by mushroom tyrosinase with an ID50 of 7.7 μg/mL (0.05 mM). Its oxidized analogue, cumic acid (p-isopropylbenzoic acid), was also characterized to inhibit this oxidation with an ID50 of 43 μg/mL (0.26 mM). These two inhibitors affect mushroom tyrosinase activity in different ways. Keywords: Cumin; cuminaldehyde; cumic acid; tyrosinase inhibitory activity; noncompetitive inhibition; Schiff base formation

Anisaldehyde characterized in the seeds of Pimpinella anisum L. (Umbelliferae), also known as aniseed, was found to inhibit the oxidation of l-3,4-dihydroxyphenylalanine (l-DOPA) by mushroom tyrosinase (EC 1.14.18.1) with an ID50 of 43 μg/mL (0.32 mM). The inhibition kinetics analyzed by a Lineweaver−Burk plot established anisaldehyde to be a noncompetitive inhibitor for this oxidation. On the basis of this finding, various related analogues were also tested in order to gain new insights into their structural functions. Keywords: Anisaldehyde; aniseed; tyrosinase inhibitor; l-DOPA; noncompetitive inhibition; Schiff base formation

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.

By bioassay-guided fractionations, quercetin was isolated as the principal tyrosinase inhibitor from the dried flowers of Heterotheca inuloides Cass (Compositae). This flavonol inhibited the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) by mushroom tyrosinase (EC 1.14.18.1) with an ID 50 of 22 μg/ml (0.07 mM). Interestingly, quercetin 3-β-glucoside did not inhibit this oxidation up to 1 mg/ml. Kinetic study have found quercetin to be a characteristic competitive inhibitor for the L-DOPA oxidation by the mushroom tyrosinase. Based on the above findings, several related flavonoids were also examined for comparison.

As a defense mechanism of the leaves of Rhus javanica (Anacardiaceae) against the aphid Melaphis chinensis (Aphididae) attack, tannic acid is rapidly accumulated and forms galls along the midrib of the leaves resulting in a unique natural medicine Gallae Rhois. Tannic acid was found to inhibit the oxidation of ʟ-3,4-dihydroxyphenylalanine (ʟ-DOPA) catalyzed by tyrosinase (EC 1.14.18.1) with an IC50 of 22 μᴍ. The aphid would detoxify the ingested toxic tannic acid to relatively nontoxic gallic acid, whereas the non-adapted pink bollworm Pectinophora gossypiella larvae are sensitive to the ingested tannic acid.

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.