Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity

Abstract

Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory activity in vitro. Among the analogs tested, compound D was the most powerful tyrosinase inhibitor (IC50 = 28.66 µg/mL), two times more active than resveratrol (IC50 = 57.05 µg/mL), followed by the analogs A, E, B, F and C, respectively. This demonstrated that the hydroxylation at C4' on the phenolic ring was the molecular modification with most importance for the observed activity.

Azastilbene Analogs as Tyrosinase Inhibitors: New Molecules with Depigmenting Potential

“…Although melanin has a mainly photoprotective function in human skin, the accumulation of an abnormal amount of melanin in different parts of the skin resulting in more pigmented patches might become an aesthetic problem [1]. Such conditions may appear due to numerous factors, including sun exposure [2], genetic factors [3], pregnancy [4], diseases [5], use of certain medicines, and others [6]. …”

“…This enzyme catalyzes two different reactions: the hydroxylation of monophenolic compounds to o -diphenols and the oxidation of the o -diphenols to o -quinones. The enzyme converts tyrosine to 3,4-dihydroxyphenylalanine (L-DOPA) and oxidizes L-DOPA to form dopaquinone, which plays a prominent part in melanin biosynthesis [6, 7] (Figure 1). The inhibition of the enzyme tyrosinase has been the subject of many studies [6–10].…”

“…The compounds utilized in the treatment of hyperpigmentation usually act as either competitive or noncompetitive inhibitors of tyrosinase, thereby blocking reaction steps of the pathway shown above, and consequently, blocking melanin synthesis [6, 7, 11]. Among the skin-lightening and depigmenting agents, magnesium-L-ascorbyl-2-phosphate, hydroxyanisole, N -acetyl-4-S-cysteaminylphenol, arbutin (hydroquinone-beta-D-glucopyranoside), salicylhydroxamic acid, dioic acid, kojic acid, and hydroquinone are the most widely used in the cosmetic industry, being prescribed worldwide [8, 12–14].…”

“…Among the skin-lightening and depigmenting agents, magnesium-L-ascorbyl-2-phosphate, hydroxyanisole, N -acetyl-4-S-cysteaminylphenol, arbutin (hydroquinone-beta-D-glucopyranoside), salicylhydroxamic acid, dioic acid, kojic acid, and hydroquinone are the most widely used in the cosmetic industry, being prescribed worldwide [8, 12–14]. However, there are reports on potential mutagenicity and epidemics of ochronosis, as well as on adverse reactions that may aggravate the appearance of the spots and damage the health of patients who make use of such agents [6, 12]. …”

“…Instead, dioic acid has been used to treat hyperpigmentation, with good efficacy, but with similar side effects as hydroquinone [19]. For that reason, there has been an increasing impetus to find alternative herbal and synthetic pharmaceutical depigmenting agents [6, 12, 17]. …”