{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:28:53Z","timestamp":1786969733775,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N42A680148"],"award-info":[{"award-number":["N42A680148"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"award":["N42A680148"],"award-info":[{"award-number":["N42A680148"]}],"id":[{"id":"https:\/\/ror.org\/018wfhg78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Tyrosinase is a key enzyme that catalyzes the rate-limiting step in melanogenesis. Although numerous mushroom-derived tyrosinase inhibitors have been identified, many exhibit limited efficacy against human tyrosinase. In this study, in silico approaches were employed to evaluate the inhibitory potential of aminonaphthoquinone\u2013chalcone hybrids against human tyrosinase. Molecular docking analysis revealed that all 10 hybrids showed higher binding affinity than kojic acid. Among them, six hybrids (3, 4, 5, 7, 9, and 10) displayed higher binding affinity than the others and interacted with amino acid residues within the active site of tyrosinase. Molecular dynamics simulations revealed that the six selected hybrids maintained stable binding to human tyrosinase throughout the simulations. Among them, compound 9 exhibited the highest structural stability, consistent with its most favorable MM\/PBSA-predicted binding free energy and the greatest number of key residue interactions (K306, K334, S358, S360, N364, H367, I368, S375, Q376, and V377). Van der Waals interactions were identified as the predominant driving force governing ligand\u2013protein binding in all complexes. These findings provide atomistic insights into the interactions between aminonaphthoquinone\u2013chalcone hybrids and human tyrosinase and may facilitate the future development of novel human tyrosinase inhibitors.<\/jats:p>","DOI":"10.3390\/ijms27167328","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"7328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural Dynamics and Susceptibility of Aminonaphthoquinone\u2013Chalcone Hybrids Against Human Tyrosinase"],"prefix":"10.3390","volume":"27","author":[{"given":"Sahachai","family":"Sabuakham","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Napat","family":"Nuramrum","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7402-3235","authenticated-orcid":false,"given":"Thanyada","family":"Rungrotmongkol","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics and Computational Biology, College of Interdisciplinary and Integrative Studies, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Structural and Computational Biology, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratchanok","family":"Pingaew","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-334X","authenticated-orcid":false,"given":"Panupong","family":"Mahalapbutr","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrm2258","article-title":"Melanosomes-dark organelles enlighten endosomal membrane transport","volume":"8","author":"Raposo","year":"2007","journal-title":"Nat. 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