{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:06:36Z","timestamp":1790805996095,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sardinia Autonomous Region, project COSMESAGRO, L.R. 7, 2007","award":["CRP 25,114"],"award-info":[{"award-number":["CRP 25,114"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u00b5M concentration. In cell proliferation assays, compounds 1, 6 and 7 did not show significant toxicity on fibroblasts nor melanoma cells up to 10 \u00b5M 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 \u00b5M, and by amperometric assay with IC50 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 \u00b5M. Moreover, the antioxidant activity of the selected inhibitors was evaluated against H2O2 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.<\/jats:p>","DOI":"10.3390\/molecules27227942","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T06:19:01Z","timestamp":1668665941000},"page":"7942","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4319-4197","authenticated-orcid":false,"given":"Gaia","family":"Rocchitta","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina, Chirurgia e Farmacia, Universit\u00e0 Degli Studi di Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6581-2227","authenticated-orcid":false,"given":"Carla","family":"Rozzo","sequence":"additional","affiliation":[{"name":"Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale Ricerche, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0649-1010","authenticated-orcid":false,"given":"Marina","family":"Pisano","sequence":"additional","affiliation":[{"name":"Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale Ricerche, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3947-5164","authenticated-orcid":false,"given":"Davide","family":"Fabbri","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8776-9271","authenticated-orcid":false,"given":"Maria Antonietta","family":"Dettori","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5596-9295","authenticated-orcid":false,"given":"Paolo","family":"Ruzza","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Honisch","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4626-4792","authenticated-orcid":false,"given":"Roberto","family":"Dallocchio","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8258-7332","authenticated-orcid":false,"given":"Alessandro","family":"Dess\u00ec","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Migheli","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina, Chirurgia e Farmacia, Universit\u00e0 Degli Studi di Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PierAndrea","family":"Serra","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina, Chirurgia e Farmacia, Universit\u00e0 Degli Studi di Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Delogu","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, Consiglio Nazionale Ricerche, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/j.1468-2494.2010.00616.x","article-title":"The melanogenesis and mechanisms of skin-lightening agents-existing and new approaches","volume":"33","author":"Gillbro","year":"2011","journal-title":"Int. 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