Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

Abstract

One of the most common approaches for control of skin pigmentation involves the inhibition of tyrosinase, a copper-containing enzyme which catalyzes the key steps of melanogenesis. This review focuses on the tyrosinase inhibition properties of a series of natural and synthetic, bioinspired phenolic compounds that have appeared in the literature in the last five years. Both mushroom and human tyrosinase inhibitors have been considered. Among the first class, flavonoids, in particular chalcones, occupy a prominent role as natural inhibitors, followed by hydroxystilbenes (mainly resveratrol derivatives). A series of more complex phenolic compounds from a variety of sources, first of all belonging to the Moraceae family, have also been described as potent tyrosinase inhibitors. As to the synthetic compounds, hydroxycinnamic acids and chalcones again appear as the most exploited scaffolds. Several inhibition mechanisms have been reported for the described inhibitors, pointing to copper chelating and/or hydrophobic moieties as key structural requirements to achieve good inhibition properties. Emerging trends in the search for novel skin depigmenting agents, including the development of assays that could distinguish between inhibitors and potentially toxic substrates of the enzyme as well as of formulations aimed at improving the bioavailability and hence the effectiveness of well-known inhibitors, have also been addressed.

“Clicking” an Ionic Liquid to a Potent Antimicrobial Peptide: On the Route towards Improved Stability

“…For instance, in a non-healing infected wound, peptides are vulnerable to modification by endogenous (e.g., tyrosinase, elastase, metalloproteinases) and exogenous (produced by colonizing microbes) enzymes in the wound site [ 23 ]. Peptide 3.1-PP4 and derivatives thereof are under investigation for topical applications on infected skin lesions; thus, to evaluate how the conjugation of an IL to 3.1-PP4 could affect the enzymatic stability of this peptide, we incubated both the conjugate and the parent peptide with tyrosinase, due to its central role in melanin biosynthesis in the skin [ 24 ], and reported increased levels in the course of wound healing [ 25 ]. The choice of this particular enzyme may seem odd at a first glance, as the 3.1-PP4 sequence lacks tyrosine residues, whereas tyrosinase is best known for promoting oxidation of phenols like, e.g., the side chain of tyrosine [ 25 ].…”

Biochemical and functional properties of wheat middlings bioprocessed by lactic acid bacteria

“…These include flavonoids, which occupy a major role as natural inhibitors, followed by hydroxystilbenes, lignans, and simple phenols such as hydroxyquinone and its derivatives. A series of more complex phenolic compounds from a variety of plant sources have been also described as potent TYR inhibitors (Panzella & Napolitano, 2019; Zolghadri et al., 2019).…”

The High Content of Ent-11α-hydroxy-15-oxo-kaur- 16-en-19-oic Acid in Adenostemma lavenia (L.) O. Kuntze Leaf Extract: With Preliminary in Vivo Assays

“…Although anti-tumor and anti-inflammatory activities are found in a variety of kaurens [7,[34][35][36], the specific feature of 11αOH-KA is a type of anti-melanogenic activity [5]. A number of natural compounds, such as flavonoids and terpenoids, have been found to modulate melanogenesis by altering the expression of microphthalmia transcription factor (MITF), which is essential for melanogenic programs [13,14]. In contrast to these compounds, no MITF modulators have been found in kaurens or kaurenoic acids.…”

“…The structural requirements for anti-inflammatory activity are similar to those for anti-cancer activity, suggesting crosstalk via common cellular targets, such as nuclear factor kappa B (NF-κB) [12]. Tyrosinase is a rate-limiting enzyme in melanin synthesis [13,14]. The enzyme catalyzes sequential reactions: the conversion of tyrosine to l-3,4-dihydroxyphenylalanine, l-Dopa, and then to dopaquinone.…”