{"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":1790805996325,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MIUR\u2014\u201cFinanziamento delle Attivit\u00e0 Base di Ricerca\u2033 FFABR UNIME"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms24097944","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T02:27:56Z","timestamp":1682648876000},"page":"7944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Leveraging the 3-Chloro-4-fluorophenyl Motif to Identify Inhibitors of Tyrosinase from Agaricus bisporus"],"prefix":"10.3390","volume":"24","author":[{"given":"Salvatore","family":"Mirabile","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D\u2019Alcontres 31, I-98166 Messina, Italy"},{"name":"Foundation Prof. Antonio Imbesi, University of Messina, Piazza Pugliatti 1, I-98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9976-0170","authenticated-orcid":false,"given":"Laura","family":"Ielo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Turin, Via P. Giuria 7, 10125 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D\u2019Alcontres 31, I-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D\u2019Alcontres 31, I-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"Gitto","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D\u2019Alcontres 31, I-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paola","family":"German\u00f2","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D\u2019Alcontres 31, I-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3037-5930","authenticated-orcid":false,"given":"Vittorio","family":"Pace","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Turin, Via P. Giuria 7, 10125 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0614-5713","authenticated-orcid":false,"given":"Laura","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D\u2019Alcontres 31, I-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114525","DOI":"10.1016\/j.ejmech.2022.114525","article-title":"Azole inhibitors of mushroom and human tyrosinases: Current advances and prospects of drug development for melanogenic dermatological disorders","volume":"239","author":"Ghani","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vaezi, M. (J. Biomol. Struct. Dyn., 2022). Structure and inhibition mechanism of some synthetic compounds and phenolic derivatives as tyrosinase inhibitors: Review and new insight, J. Biomol. Struct. 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