Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

The Role of Tyrosinase in Human Health and Disease

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 11660

Share This Special Issue

Special Issue Editor

Dr. Laura Ielo

E-Mail Website
Guest Editor

Department of Chemistry, University of Turin, Via P. Giuria 7, 10125 Turin, Italy
Interests: tyrosinase inhibitors; synthesis; organometallic chemistry; medicinal chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, the development of tyrosinase inhibitors (TYRIs) as plausible agents useful for the treatment of skin diseases is playing a central role in research. Tyrosinase (TYR) is a type 3 copper-containing enzyme widely distributed in nature (bacteria, fungi, mammals, and plants). It is involved in the mammal biosynthesis of melanin catalysing the first two steps of the synthetic process, the hydroxylation of L-tyrosine to L-DOPA and the subsequent oxidation of L-DOPA to L-dopaquinone. Therefore, TYR performs a crucial role in skin, hair, eyes pigmentation and in skin protection from UV radiations. In particular, in humans, the abnormal lack of melanin could be responsible of albinism; on the other hand, an excessive accumulation of melanin can cause disorders related to hyperpigmentation. In fact, TYRIs are considered potential skin-whitening agents, antimelanogenic substances for melanoma treatment. Furthermore, TYRIs could be innovative adjuvants in Parkinson’s disease therapies related to neurodegenerative effects of neuromelanin, as well as drugs for bacterial infections. Papers related to any aspect of TYR role in human health and disease, will be considered for this Special Issue. Experimental and bioinformatics papers, up-to-date review articles, and commentaries are also welcome.

This Special Issue is supervised by Dr. Laura Ielo and assisted by our Topical Advisory Panel Member Dr. Serena Vittorio (Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli, 25, I-20133 Milano, Italy).

Dr. Laura Ielo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

tyrosinase inhibitors
in silico studies
in vivo studies
in vitro studies
synthesis
natural products
skin diseases
crystal structures

Published Papers (6 papers)

Download All Papers

Research

Jump to: Review

15 pages, 3251 KiB

Open AccessArticle

Leveraging the 3-Chloro-4-fluorophenyl Motif to Identify Inhibitors of Tyrosinase from Agaricus bisporus

by Salvatore Mirabile, Laura Ielo, Lisa Lombardo, Federico Ricci, Rosaria Gitto, Maria Paola Germanò, Vittorio Pace and Laura De Luca

Int. J. Mol. Sci. 2023, 24(9), 7944; https://doi.org/10.3390/ijms24097944 - 27 Apr 2023

Cited by 1 | Viewed by 1251

Abstract

Tyrosinase (EC 1.14.18.1) is implicated in melanin production in various organisms. There is a growing body of evidence suggesting that the overproduction of melanin might be related to several skin pigmentation disorders as well as neurodegenerative processes in Parkinson’s disease. Based on this consideration, the development of tyrosinase inhibitors represents a new challenge to identify new agents in pharmaceutical and cosmetic applications. With the goal of identifying tyrosinase inhibitors from a synthetic source, we employed a cheap and facile preliminary assay using tyrosinase from Agaricus bisporus (AbTYR). We have previously demonstrated that the 4-fluorobenzyl moiety might be effective in interactions with the catalytic site of AbTYR; moreover, the additional chlorine atom exerted beneficial effects in enhancing inhibitory activity. Therefore, we planned the synthesis of new small compounds in which we incorporated the 3-chloro-4-fluorophenyl fragment into distinct chemotypes that revealed the ability to establish profitable contact with the AbTYR catalytic site. Our results confirmed that the presence of this fragment is an important structural feature to improve the AbTYR inhibition in these new chemotypes as well. Furthermore, docking analysis supported the best activity of the selected studied compounds, possessing higher potency when compared with reference compounds. Full article

(This article belongs to the Special Issue The Role of Tyrosinase in Human Health and Disease)

► Show Figures

Figure 1

19 pages, 2063 KiB

Open AccessArticle

Inhibitory Activities of Samples on Tyrosinases Were Affected by Enzyme Species and Sample Addition Methods

by Wei Wang, Lijuan Yang, Weiwei Wang, Jianyong Zhang, Ulrich H. Engelhardt and Heyuan Jiang

Int. J. Mol. Sci. 2023, 24(7), 6013; https://doi.org/10.3390/ijms24076013 - 23 Mar 2023

Viewed by 1215

Abstract

The inhibition of tyrosinase (TYR) activity is an effective measure to inhibit melanin synthesis. At present, there are many methods with discrepant details that study the TYR inhibitory activity of samples. Under the same experimental conditions, this paper systematically studies whether enzyme species and sample addition methods are the key factors that determine the TYR inhibitory activity of samples. TYRs extracted from B16F10 cells, apple and mushroom, called BTYR, ATYR and MTYR, respectively, were selected to implement this study. Results showed that TYR inhibitory activities of samples were obviously affected by the above two factors. It was necessary to select the appropriate enzyme according to the problems to be explained. It was speculated that indirectly inhibitory activity reflected the comprehensive effects of samples on TYR catalytic activity and intracellular TYR synthesis pathway, while directly inhibitory activity reflected the effects of samples on TYR catalytic activity. Additionally, kojic acid could be used as a positive control for both B16F10 cells and MTYR models. The TYR inhibitory activity of β-arbutin was complicated and fickle, while that of epigallocatechin gallate (EGCG) was universal and stable, which is to say, EGCG always inhibited TYR activity in a dose-dependent manner. In conclusion, the TYR inhibitory activities of samples were affected by enzyme species and sample addition methods. Compared with the unstable β-arbutin, EGCG was more valuable for clinical research. Full article

(This article belongs to the Special Issue The Role of Tyrosinase in Human Health and Disease)

► Show Figures

Graphical abstract

22 pages, 6420 KiB

Open AccessArticle

Coumarin-Based Compounds as Inhibitors of Tyrosinase/Tyrosine Hydroxylase: Synthesis, Kinetic Studies, and In Silico Approaches

by Jéssica Alves Nunes, Rodrigo Santos Aquino de Araújo, Fabrícia Nunes da Silva, Joanna Cytarska, Krzysztof Z. Łączkowski, Sílvia Helena Cardoso, Francisco Jaime Bezerra Mendonça-Júnior and Edeildo Ferreira da Silva-Júnior

Int. J. Mol. Sci. 2023, 24(6), 5216; https://doi.org/10.3390/ijms24065216 - 9 Mar 2023

Cited by 7 | Viewed by 2025

Abstract

Cancer represents the main cause of morbidity and mortality worldwide, constituting a serious health problem. In this context, melanoma represents the most aggressive and fatal type of skin cancer, with death rates increasing every year. Scientific efforts have been addressed to the development of inhibitors targeting the tyrosinase enzyme as potential anti-melanoma agents due to the importance of this enzyme in melanogenesis biosynthesis. Coumarin-based compounds have shown potential activity as anti-melanoma agents and tyrosinase inhibitors. In this study, coumarin-based derivatives were designed, synthesized, and experimentally evaluated upon tyrosinase. Compound FN-19, a coumarin–thiosemicarbazone analog, exhibited potent anti-tyrosinase activity, with an IC₅₀ value of 42.16 ± 5.16 µM, being more active than ascorbic acid and kojic acid, both reference inhibitors. The kinetic study showed that FN-19 acts as a mixed inhibitor. Still, for this compound, molecular dynamics (MD) simulations were performed to determine the stability of the complex with tyrosinase, generating RMSD, RMSF, and interaction plots. Additionally, docking studies were performed to elucidate the binding pose at the tyrosinase, suggesting that the hydroxyl group of coumarin derivative performs coordinate bonds (bidentate) with the copper(II) ions at distances ranging from 2.09 to 2.61 Å. Then, MM/PBSA calculations revealed that van der Waals interactions are the most relevant intermolecular forces for complex stabilization. Furthermore, it was observed that FN-19 has a binding energy (ΔE_MM) value similar to tropolone, a tyrosinase inhibitor. Therefore, the data obtained in this study will be useful for designing and developing novel coumarin-based analogs targeting the tyrosinase enzyme. Full article

(This article belongs to the Special Issue The Role of Tyrosinase in Human Health and Disease)

► Show Figures

Figure 1

19 pages, 4861 KiB

Open AccessArticle

Computer-Aided Virtual Screening and In Vitro Validation of Biomimetic Tyrosinase Inhibitory Peptides from Abalone Peptidome

by Sasikarn Kongsompong, Teerasak E-kobon, Weerasak Taengphan, Mattanun Sangkhawasi, Mattaka Khongkow and Pramote Chumnanpuen

Int. J. Mol. Sci. 2023, 24(4), 3154; https://doi.org/10.3390/ijms24043154 - 5 Feb 2023

Cited by 4 | Viewed by 2379

Abstract

Hyperpigmentation is a medical and cosmetic problem caused by an excess accumulation of melanin or the overexpression of the enzyme tyrosinase, leading to several skin disorders, i.e., freckles, melasma, and skin cancer. Tyrosinase is a key enzyme in melanogenesis and thus a target for reducing melanin production. Although abalone is a good source of bioactive peptides that have been used for several properties including depigmentation, the available information on the anti-tyrosinase property of abalone peptides remains insufficient. This study investigated the anti-tyrosinase properties of Haliotis diversicolor tyrosinase inhibitory peptides (hdTIPs) based on mushroom tyrosinase, cellular tyrosinase, and melanin content assays. The binding conformation between peptides and tyrosinase was also examined by molecular docking and dynamics study. KNN1 showed a high potent inhibitory effect on mushroom tyrosinase with an IC₅₀ of 70.83 μM. Moreover, our selected hdTIPs could inhibit melanin production through the reductions in tyrosinase activity and reactive oxygen species (ROS) levels by enhancing the antioxidative enzymes. RF1 showed the highest activity on both cellular tyrosinase inhibition and ROS reduction. leading to the lower melanin content in B16F10 murine melanoma cells. Accordingly, it can be assumed that our selected peptides exhibited high potential in medical cosmetology applications. Full article

(This article belongs to the Special Issue The Role of Tyrosinase in Human Health and Disease)

► Show Figures

Figure 1

16 pages, 2887 KiB

Open AccessArticle

Hydroxylated Coumarin-Based Thiosemicarbazones as Dual Antityrosinase and Antioxidant Agents

by Sebastiano Masuri, Benedetta Era, Francesca Pintus, Enzo Cadoni, Maria Grazia Cabiddu, Antonella Fais and Tiziana Pivetta

Int. J. Mol. Sci. 2023, 24(2), 1678; https://doi.org/10.3390/ijms24021678 - 14 Jan 2023

Cited by 8 | Viewed by 1742

Abstract

The design of novel antityrosinase agents appears extremely important in medical and industrial sectors because an irregular production of melanin is related to the insurgence of several skin-related disorders (e.g., melanoma) and the browning process of fruits and vegetables. Because melanogenesis also involves a nonenzymatic oxidative process, developing dual antioxidant and antityrosinase agents is advantageous. In this work, we evaluated the antioxidant and tyrosinase inhibition ability of two new bishydroxylated and two new monohydroxylated derivatives of (1E)-2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazine-1-carbothioamide (T1) using different experimental and computational approaches. The study was also carried out on another monohydroxylated derivative of T1 for comparison. Interestingly, these molecules have more potent tyrosinase-inhibitory properties than the reference compound, kojic acid. Moreover, the antioxidant activity appears to be influenced according to the number and substitution pattern of the hydroxyl groups. The safety of the compounds without (T1), with one (T3), and with two (T6) hydroxyl groups, has also been assessed by studying their cytotoxicity on melanocytes. These results indicate that (1E)-2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazine-1-carbothioamide and its hydroxylated derivatives are promising molecules for further drug development studies. Full article

(This article belongs to the Special Issue The Role of Tyrosinase in Human Health and Disease)

► Show Figures

Figure 1

Review

Jump to: Research

49 pages, 15227 KiB

Open AccessReview

Heterocyclic Compounds as Synthetic Tyrosinase Inhibitors: Recent Advances

by Serena Vittorio, Christian Dank and Laura Ielo

Int. J. Mol. Sci. 2023, 24(10), 9097; https://doi.org/10.3390/ijms24109097 - 22 May 2023

Cited by 7 | Viewed by 1910

Abstract

Tyrosinase is a copper-containing enzyme which is widely distributed in nature (e.g., bacteria, mammals, fungi) and involved in two consecutive steps of melanin biosynthesis. In humans, an excessive production of melanin can determine hyperpigmentation disorders as well as neurodegenerative processes in Parkinson’s disease. The development of molecules able to inhibit the high activity of the enzyme remain a current topic in medicinal chemistry, because the inhibitors reported so far present several side effects. Heterocycle-bearing molecules are largely diffuse in this sense. Due to their importance as biologically active compounds, we decided to report a comprehensive review of synthetic tyrosinase inhibitors possessing heterocyclic moieties reported within the last five years. For the reader’s convenience, we classified them as inhibitors of mushroom tyrosinase (Agaricus bisporus) and human tyrosinase. Full article

(This article belongs to the Special Issue The Role of Tyrosinase in Human Health and Disease)

► Show Figures