Inhibition of Mushroom Tyrosinase Activity by Orsellinates

Abstract

Several applications have been proposed for tyrosinase inhibitors in the pharmaceutical, food bioprocessing, and environmental industries. However, only a few compounds are known to serve as effective tyrosinase inhibitors. This study evaluated the tyrosinase-related activity of resorcinol (1), orcinol (2) lecanoric acid (3), and derivatives of this acid (4-15). Subjected to alcoholysis, lecanoric acid (3), a depside isolated from the lichen Parmotrema tinctorum, produces orsellinic acid (2,4-dihydroxy-6-methylbenzoic acid) (4) and orsellinates (2,4-dihydroxy-6-methyl benzoates) (5-15). At 0.50 mM, methyl (5), ethyl (6), n-propyl (7), tert-butyl (11), and n-cetyl orsellinates (15) acted as tyrosinase activators, whereas n-butyl (8), iso-propyl (9), sec-butyl (10), n-pentyl (12), n-hexyl (13), and n-octyl orsellinates (14) behaved as inhibitors. Tyrosinase inhibition rose with chain elongation-n-butyl (8)<n-pentyl (12)<n-hexyl (13)<n-octyl orsellinates (14)-suggesting that the enzyme site can accept an eight-carbon alkyl chain. A kinetic study of n-octyl orsellinate (14) revealed uncompetitive inhibition of tyrosinase, with an inhibition constant of 0.99 mM. Key words tyrosinase; orsellinate; lecanoric acid; Parmotrema tinctorumTyrosinase (EC 1.14.18.1) is a copper enzyme that catalyzes both the hydroxylation of monophenols to o-diphenols and the oxidation of o-diphenols to o-quinones.1,2) o-Quinones are highly reactive compounds that can polymerize spontaneously to form high-molecular-weight compounds, such as melanin. In humans, melanin protects the skin against UV radiation, but its overproduction can result in malignant melanoma.3) In foods, o-quinones can react with amino acids and/or proteins, conferring enhanced brownish coloration and affecting the organoleptic properties and appearance of foodstuffs. 4)

A comprehensive review on tyrosinase inhibitors

“…The most common hydroxycinnamates are p -coumaric, caffeic and ferulic acids. So far, p -hydroxybenzoic acid, chlorogenic acid (the ester of caffeic acid ), vanilic acid (4-hydroxy-3-methoxybenzoic acid) and protocatechuic acid (a dihydroxybenzoic acid) from Hypericum laricifolium Juss 154 , protocatechualdehyde (IC 50 = 0.40 µg/mL) from Phellinus linteus 175 , benzoic acid propyl gallate 309 , orsellinic acid (2,4-dihydroxy-6-methylbenzoic acid) and orsellinates (2,4-dihydroxy-6-methyl benzoates) 310 , p -coumaric acid from ginseng leaves 311 , m -coumaric acid 312 , p -coumarate 313 and its derivatives from leaves of Breynia officinalis 184 caffeic acid and its n -nonyl ester 314 , ferulic acid from Spiranthes sinensis 224 , 4-Hydroxy cinnamic acid 315 , synthetic hydroxycinnamoyl phenylalanyl/prolyl hydroxamic acid derivatives 316 , and seven hydroxycinnamoyl derivatives in green coffee beans 317 have been investigated for their tyrosinase inhibition activity. Among these, propyl gallate is a reversible and mixed-type inhibitor on diphenolase activity of tyrosinase with K IS = 2.135 mM and K i = 0.661 mM 309 .…”

A Combination of Pharmacophore and Docking‐based Virtual Screening to Discover new Tyrosinase Inhibitors

“…Its active site is well conserved among the different species, it is characterized by the presence of two copper ions, usually referred to as CuA and CuB, each coordinated by three histidine residues . In presence of molecular oxygen, tyrosinase catalyzes the hydroxylation of tyrosine to L‐Dopa and the subsequent oxidation of L‐Dopa to dopaquinone, which polymerize spontaneously to form melanin pigments …”

“…[3] In presence of molecular oxygen, tyrosinase catalyzes the hydroxylation of tyrosine to L-Dopa and the subsequent oxidation of L-Dopa to dopaquinone, [2] which polymerize spontaneously to form melanin pigments. [4] Targeting tyrosinase is the most prominent approach to inhibit melanogenesis to obtain therapeutics for the treatment of hyperpigmentary disorders. Many tyrosinase inhibitors (TyIs) have been reported in literature so far both from synthetic and natural sources, but their use is limited by their side effects, lack of stability and cytotoxicity.…”

Depigmenting potential of lichen extracts evaluated by in vitro and in vivo tests

“…Therefore, further work is necessary to isolate and quantify active compounds from the extracts in order to better define the components with antityrosinase activity. So far, several works have investigated the possible antityrosinase activity of lichen compounds (e.g., Kwong et al, 2020;Honda et al, 2016;Lopes, Coelho & Honda, 2018). For example, Kim & Cho (2007) determined that methanolic extracts of Usnea longissima and Usnea esculenta affected melanin formation independently from their antioxidant action.…”

“…For many of these compounds the inhibitory activity has been related to their phenolic structure that provides high antioxidant power. Various pieces of evidence indicate that lichens are worth being investigated as possible sources of this kind of compounds (Brandão et al, 2017;Higuchi et al, 1993;Honda et al, 2016;Lopes, Coelho & Honda, 2018).…”