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...
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/22/7942 |
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| author | Gaia Rocchitta Carla Rozzo Marina Pisano Davide Fabbri Maria Antonietta Dettori Paolo Ruzza Claudia Honisch Roberto Dallocchio Alessandro Dessì Rossana Migheli PierAndrea Serra Giovanna Delogu |
| author_facet | Gaia Rocchitta Carla Rozzo Marina Pisano Davide Fabbri Maria Antonietta Dettori Paolo Ruzza Claudia Honisch Roberto Dallocchio Alessandro Dessì Rossana Migheli PierAndrea Serra Giovanna Delogu |
| author_sort | Gaia Rocchitta |
| collection | DOAJ |
| 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 <b>1</b>, <b>6</b> and <b>7</b> 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 <b>1</b>, <b>6</b> and <b>7</b>, showed values around 80% at 5 µM concentration. In cell proliferation assays, compounds <b>1</b>, <b>6</b> and <b>7</b> 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<sub>50</sub> for compounds <b>1</b>, <b>6</b> and <b>7</b> 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 <b>7</b> 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<sub>2</sub>O<sub>2</sub> in amperometric experiments, whereby compound <b>7</b> was about three times more effective compared to compounds <b>1</b> and <b>6</b>. The tyrosinase X-ray structure of <i>Bacterium megaterium</i> crystal was used to carry out molecular docking studies in the presence of compounds <b>1</b>, <b>6</b> and <b>7</b> in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds <b>6</b> and <b>7</b> confirmed the high affinity of these compounds to tyrosinase protein. |
| first_indexed | 2024-03-09T18:07:31Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:07:31Z |
| publishDate | 2022-11-01 |
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| spelling | doaj.art-f9ba52cca3de45669dd6e8b3582376c52023-11-24T09:23:47ZengMDPI AGMolecules1420-30492022-11-012722794210.3390/molecules27227942Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and MelanogenesisGaia Rocchitta0Carla Rozzo1Marina Pisano2Davide Fabbri3Maria Antonietta Dettori4Paolo Ruzza5Claudia Honisch6Roberto Dallocchio7Alessandro Dessì8Rossana Migheli9PierAndrea Serra10Giovanna Delogu11Dipartimento di Medicina, Chirurgia e Farmacia, Università Degli Studi di Sassari, 07100 Sassari, ItalyIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale Ricerche, 07100 Sassari, ItalyIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale Ricerche, 07100 Sassari, ItalyIstituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 07100 Sassari, ItalyIstituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 07100 Sassari, ItalyIstituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 35131 Padova, ItalyIstituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 35131 Padova, ItalyIstituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 07100 Sassari, ItalyIstituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 07100 Sassari, ItalyDipartimento di Medicina, Chirurgia e Farmacia, Università Degli Studi di Sassari, 07100 Sassari, ItalyDipartimento di Medicina, Chirurgia e Farmacia, Università Degli Studi di Sassari, 07100 Sassari, ItalyIstituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 07100 Sassari, ItalyTyrosinase 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 <b>1</b>, <b>6</b> and <b>7</b> 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 <b>1</b>, <b>6</b> and <b>7</b>, showed values around 80% at 5 µM concentration. In cell proliferation assays, compounds <b>1</b>, <b>6</b> and <b>7</b> 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<sub>50</sub> for compounds <b>1</b>, <b>6</b> and <b>7</b> 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 <b>7</b> 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<sub>2</sub>O<sub>2</sub> in amperometric experiments, whereby compound <b>7</b> was about three times more effective compared to compounds <b>1</b> and <b>6</b>. The tyrosinase X-ray structure of <i>Bacterium megaterium</i> crystal was used to carry out molecular docking studies in the presence of compounds <b>1</b>, <b>6</b> and <b>7</b> in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds <b>6</b> and <b>7</b> confirmed the high affinity of these compounds to tyrosinase protein.https://www.mdpi.com/1420-3049/27/22/7942tyrosinase inhibitorssustainable synthesiscurcumin-inspired derivativesmelanogenesisin silico analysesbiosensors |
| spellingShingle | Gaia Rocchitta Carla Rozzo Marina Pisano Davide Fabbri Maria Antonietta Dettori Paolo Ruzza Claudia Honisch Roberto Dallocchio Alessandro Dessì Rossana Migheli PierAndrea Serra Giovanna Delogu Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis Molecules tyrosinase inhibitors sustainable synthesis curcumin-inspired derivatives melanogenesis in silico analyses biosensors |
| 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 | tyrosinase inhibitors sustainable synthesis curcumin-inspired derivatives melanogenesis in silico analyses biosensors |
| url | https://www.mdpi.com/1420-3049/27/22/7942 |
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