Melanin pigmentation control by 1,3‐thiazolidines: does <scp>NO</scp> scavenging play a critical role?

Napolitano, Alessandra; Micillo, Raffaella; Monfrecola, Giuseppe

doi:10.1111/exd.13033

Cited by 5 publications

(3 citation statements)

References 11 publications

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“…In this way dopaquinone is subtracted from the melanogenic pathway and a decrease of pigmentation is observed though the activity of the enzyme that has not been affected to any extent. This could be the case of compounds comprising a resorcinol moiety [230], like phenylethyl resorcinol and resveratrol derivatives, or a thiazolidine unit that may undergo ring opening disclosing the thiol functionality [231]. Of course, the possible toxicity associated with the occurrence of this diverted reaction pathways should be carefully evaluated.…”

Section: New Trends In the Search For Tyrosinase Inhibitorsmentioning

confidence: 99%

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

2019

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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.

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Section: New Trends In the Search For Tyrosinase Inhibitorsmentioning

confidence: 99%

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

2019

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“…These two compounds were identified to be potent competitive tyrosinase inhibitors and to effectively reduce melanogenesis in HRM2 hairless mice 10,11. In addition to directly inhibiting tyrosinase activity, MHY384 inhibited tyrosinase expression by suppressing the cyclic adenosine monophosphate–PKA10 and NO-induced cyclic guanosine monophosphate–PKG12,13 pathways, and MHY794 also suppressed tyrosinase expression induced by NO-mediated melanogenesis signaling 11. These positive results and the fact that divalent –S– is a classical isostere of divalent –NH– encouraged us to synthesize derivatives with a dithiolane ring as a surrogate for the thiazolidine ring commonly existing in MHY384 and MHY794, in order to find novel tyrosinase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and antimelanogenic effects of (2-substituted phenyl-1,3-dithiolan-4-yl)methanol derivatives

Kim

Ullah

et al. 2017

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The authors designed and synthesized 17 (2-substituted phenyl-1,3-dithiolan-4-yl) methanol (PDTM) derivatives to find a new chemical scaffold, showing excellent tyrosinase-inhibitory activity. Their tyrosinase-inhibitory activities were evaluated against mushroom tyrosinase at 50 μM, and five of the PDTM derivatives (PDTM3, PDTM7–PDTM9, and PDTM13) were found to inhibit mushroom tyrosinase more than kojic acid or arbutin, the positive controls. Of seventeen PDTMs, PDTM3 (half-maximal inhibitory concentration 13.94±1.76 μM), with a 2,4-dihydroxyphenyl moiety, exhibited greatest inhibitory effects (kojic acid half-maximal inhibitory concentration 18.86±2.14 μM). Interestingly, PDTM compounds with no hydroxyl group, PDTM7–PDTM9, also had stronger inhibitory activities than kojic acid. In silico studies of interactions between tyrosinase and the five PDTMs suggested their binding affinities were closely related to their tyrosinase-inhibitory activities. Cell-based experiments performed using B16F10 mouse-skin melanoma cells showed that PDTM3 effectively inhibited melanogenesis and cellular tyrosinase activity. A cell-viability study conducted using B16F10 cells indicated that the antimelanogenic effect of PDTM3 was not attributable to its cytotoxicity. Kinetic studies showed PDTM3 competitively inhibited tyrosinase, indicating binding to the tyrosinase-active site. We found that PDTM3 with a new chemical scaffold could be a promising candidate for skin-whitening agents, and that the 1,3-dithiolane ring could be used as a chemical scaffold for potent tyrosinase inhibition.

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“… Schematic diagram representing major signaling pathways involved in the expression of melanogenic enzymes [ 29 , 30 , 31 , 32 , 33 , 34 ]. …”

Section: Figurementioning

confidence: 99%

Hypopigmenting Effects of Brown Algae-Derived Phytochemicals: A Review on Molecular Mechanisms

et al. 2017

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There is a rapid increase in the demand for natural hypopigmenting agents from marine sources for cosmeceutical and pharmaceutical applications. Currently, marine macroalgae are considered as a safe and effective source of diverse bioactive compounds. Many research groups are exploring marine macroalgae to discover and characterize novel compounds for cosmeceutical, nutraceutical, and pharmaceutical applications. Many types of bioactive secondary metabolites from marine algae, including phlorotannins, sulfated polysaccharides, carotenoids, and meroterpenoids, have already been documented for their potential applications in the pharmaceutical industry. Among these metabolites, phlorotannins from brown algae have been widely screened for their pharmaceutical and hypopigmenting effects. Unfortunately, the majority of these articles did not have detailed investigations on molecular targets, which is critical to fulfilling the criteria for their cosmeceutical and pharmaceutical use. Very recently, a few meroterpenoids have been discovered from Sargassum sp., with the examination of their anti-melanogenic properties and mechanisms. Despite the scarcity of in vivo and clinical investigations of molecular mechanistic events of marine algae-derived hypopigmenting agents, identifying the therapeutic targets and their validation in humans has been a major challenge for future studies. In this review, we focused on available data representing molecular mechanisms underlying hypopigmenting properties of potential marine brown alga-derived compounds.

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Melanin pigmentation control by 1,3‐thiazolidines: does NO scavenging play a critical role?

Cited by 5 publications

References 11 publications

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

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

Design, synthesis, and antimelanogenic effects of (2-substituted phenyl-1,3-dithiolan-4-yl)methanol derivatives

Hypopigmenting Effects of Brown Algae-Derived Phytochemicals: A Review on Molecular Mechanisms

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