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a serious health problem. In this context, melanoma represents the most aggressive and fatal type of skin cancer, with death rates increasing every year. Scientific efforts have been addressed to the development of inhibitors targeting the tyrosinase enzyme as potential anti-melanoma agents due to the importance of this enzyme in melanogenesis biosynthesis. Coumarin-based compounds have shown potential activity as anti-melanoma agents and tyrosinase inhibitors. In this study, coumarin-based derivatives were designed, synthesized, and experimentally evaluated upon tyrosinase. Compound FN-19, a coumarin\u2013thiosemicarbazone analog, exhibited potent anti-tyrosinase activity, with an IC50 value of 42.16 \u00b1 5.16 \u00b5M, being more active than ascorbic acid and kojic acid, both reference inhibitors. The kinetic study showed that FN-19 acts as a mixed inhibitor. Still, for this compound, molecular dynamics (MD) simulations were performed to determine the stability of the complex with tyrosinase, generating RMSD, RMSF, and interaction plots. Additionally, docking studies were performed to elucidate the binding pose at the tyrosinase, suggesting that the hydroxyl group of coumarin derivative performs coordinate bonds (bidentate) with the copper(II) ions at distances ranging from 2.09 to 2.61 \u00c5. Then, MM\/PBSA calculations revealed that van der Waals interactions are the most relevant intermolecular forces for complex stabilization. Furthermore, it was observed that FN-19 has a binding energy (\u0394EMM) value similar to tropolone, a tyrosinase inhibitor. Therefore, the data obtained in this study will be useful for designing and developing novel coumarin-based analogs targeting the tyrosinase enzyme.<\/jats:p>","DOI":"10.3390\/ijms24065216","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T02:33:16Z","timestamp":1678329196000},"page":"5216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Coumarin-Based Compounds as Inhibitors of Tyrosinase\/Tyrosine Hydroxylase: Synthesis, Kinetic Studies, and In Silico Approaches"],"prefix":"10.3390","volume":"24","author":[{"given":"J\u00e9ssica Alves","family":"Nunes","sequence":"first","affiliation":[{"name":"Biological and Molecular Chemistry Research Group, Institute of Chemistry and Biotechnology, Federal University of Alagoas, AC Sim\u00f5es Campus, Lourival Melo Mota Avenue, s\/n, Macei\u00f3 57072-970, Alagoas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2403-8746","authenticated-orcid":false,"given":"Rodrigo Santos Aquino de","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Para\u00edba, Jo\u00e3o Pessoa 58429-500, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabr\u00edcia Nunes da","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Medicinal Synthesis, Federal University of Alagoas, Campus Arapiraca, Manoel Severino Barbosa Avenue, Arapiraca 57309-005, Alagoas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5313-6812","authenticated-orcid":false,"given":"Joanna","family":"Cytarska","sequence":"additional","affiliation":[{"name":"Department of Chemical Technology and Pharmaceuticals, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-089 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2107-2719","authenticated-orcid":false,"given":"Krzysztof Z.","family":"\u0141\u0105czkowski","sequence":"additional","affiliation":[{"name":"Department of Chemical Technology and Pharmaceuticals, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-089 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8038-2007","authenticated-orcid":false,"given":"S\u00edlvia Helena","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Medicinal Synthesis, Federal University of Alagoas, Campus Arapiraca, Manoel Severino Barbosa Avenue, Arapiraca 57309-005, Alagoas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-833X","authenticated-orcid":false,"given":"Francisco Jaime Bezerra","family":"Mendon\u00e7a-J\u00fanior","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Para\u00edba, Jo\u00e3o Pessoa 58429-500, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1527-4501","authenticated-orcid":false,"given":"Edeildo Ferreira da","family":"Silva-J\u00fanior","sequence":"additional","affiliation":[{"name":"Biological and Molecular Chemistry Research Group, Institute of Chemistry and Biotechnology, Federal University of Alagoas, AC Sim\u00f5es Campus, Lourival Melo Mota Avenue, s\/n, Macei\u00f3 57072-970, Alagoas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022, December 20). 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