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Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis
Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695798/ https://www.ncbi.nlm.nih.gov/pubmed/36432043 http://dx.doi.org/10.3390/molecules27227942 |
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author | Rocchitta, Gaia Rozzo, Carla Pisano, Marina Fabbri, Davide Dettori, Maria Antonietta Ruzza, Paolo Honisch, Claudia Dallocchio, Roberto Dessì, Alessandro Migheli, Rossana Serra, PierAndrea Delogu, Giovanna |
author_facet | Rocchitta, Gaia Rozzo, Carla Pisano, Marina Fabbri, Davide Dettori, Maria Antonietta Ruzza, Paolo Honisch, Claudia Dallocchio, Roberto Dessì, Alessandro Migheli, Rossana Serra, PierAndrea Delogu, Giovanna |
author_sort | Rocchitta, Gaia |
collection | PubMed |
description | Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared in yields ranging from 60 to 88 % and spectrophotometric, electrochemical, in vitro and in silico analyses were carried out. The viability of PC12 cells, a rat pheochromocytoma derived-cell line, with compounds 1, 6 and 7, showed values around 80% at 5 µM concentration. In cell proliferation assays, compounds 1, 6 and 7 did not show significant toxicity on fibroblasts nor melanoma cells up to 10 µM with viability values over 90%. The inhibition of tyrosinase activity was evaluated both by a UV-Vis spectroscopic method at two different concentrations, 0.2 and 2.0 µM, and by amperometric assay with IC(50) for compounds 1, 6 and 7 ranging from 11 to 24 nM. Melanin content assays on human melanoma cells were performed to test the capability of compounds to inhibit melanin biosynthesis. All compounds exerted a decrease in melanin content, with compound 7 being the most effective by showing a melanogenesis inhibition up to four times greater than arbutin at 100 µM. Moreover, the antioxidant activity of the selected inhibitors was evaluated against H(2)O(2) in amperometric experiments, whereby compound 7 was about three times more effective compared to compounds 1 and 6. The tyrosinase X-ray structure of Bacterium megaterium crystal was used to carry out molecular docking studies in the presence of compounds 1, 6 and 7 in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds 6 and 7 confirmed the high affinity of these compounds to tyrosinase protein. |
format | Online Article Text |
id | pubmed-9695798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96957982022-11-26 Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis Rocchitta, Gaia Rozzo, Carla Pisano, Marina Fabbri, Davide Dettori, Maria Antonietta Ruzza, Paolo Honisch, Claudia Dallocchio, Roberto Dessì, Alessandro Migheli, Rossana Serra, PierAndrea Delogu, Giovanna Molecules Article Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared in yields ranging from 60 to 88 % and spectrophotometric, electrochemical, in vitro and in silico analyses were carried out. The viability of PC12 cells, a rat pheochromocytoma derived-cell line, with compounds 1, 6 and 7, showed values around 80% at 5 µM concentration. In cell proliferation assays, compounds 1, 6 and 7 did not show significant toxicity on fibroblasts nor melanoma cells up to 10 µM with viability values over 90%. The inhibition of tyrosinase activity was evaluated both by a UV-Vis spectroscopic method at two different concentrations, 0.2 and 2.0 µM, and by amperometric assay with IC(50) for compounds 1, 6 and 7 ranging from 11 to 24 nM. Melanin content assays on human melanoma cells were performed to test the capability of compounds to inhibit melanin biosynthesis. All compounds exerted a decrease in melanin content, with compound 7 being the most effective by showing a melanogenesis inhibition up to four times greater than arbutin at 100 µM. Moreover, the antioxidant activity of the selected inhibitors was evaluated against H(2)O(2) in amperometric experiments, whereby compound 7 was about three times more effective compared to compounds 1 and 6. The tyrosinase X-ray structure of Bacterium megaterium crystal was used to carry out molecular docking studies in the presence of compounds 1, 6 and 7 in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds 6 and 7 confirmed the high affinity of these compounds to tyrosinase protein. MDPI 2022-11-16 /pmc/articles/PMC9695798/ /pubmed/36432043 http://dx.doi.org/10.3390/molecules27227942 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rocchitta, Gaia Rozzo, Carla Pisano, Marina Fabbri, Davide Dettori, Maria Antonietta Ruzza, Paolo Honisch, Claudia Dallocchio, Roberto Dessì, Alessandro Migheli, Rossana Serra, PierAndrea Delogu, Giovanna Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis |
title | Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis |
title_full | Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis |
title_fullStr | Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis |
title_full_unstemmed | Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis |
title_short | Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis |
title_sort | inhibitory effect of curcumin-inspired derivatives on tyrosinase activity and melanogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695798/ https://www.ncbi.nlm.nih.gov/pubmed/36432043 http://dx.doi.org/10.3390/molecules27227942 |
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