Anilino-1,4-naphthoquinones as potent mushroom tyrosinase inhibitors: in vitro and in silico studies

Tyrosinase, a pivotal enzyme in melanin synthesis, is a primary target for the development of depigmenting agents. In this work, in vitro and in silico techniques were employed to identify novel tyrosinase inhibitors from a set of 12 anilino-1,4-naphthoquinone derivatives. Results from the mushroom...

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Main Authors: Sahachai Sabuakham, Sutita Nasoontorn, Napat Kongtaworn, Thanyada Rungrotmongkol, Atit Silsirivanit, Ratchanok Pingaew, Panupong Mahalapbutr
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
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Online Access:https://www.tandfonline.com/doi/10.1080/14756366.2024.2357174
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author Sahachai Sabuakham
Sutita Nasoontorn
Napat Kongtaworn
Thanyada Rungrotmongkol
Atit Silsirivanit
Ratchanok Pingaew
Panupong Mahalapbutr
author_facet Sahachai Sabuakham
Sutita Nasoontorn
Napat Kongtaworn
Thanyada Rungrotmongkol
Atit Silsirivanit
Ratchanok Pingaew
Panupong Mahalapbutr
author_sort Sahachai Sabuakham
collection DOAJ
description Tyrosinase, a pivotal enzyme in melanin synthesis, is a primary target for the development of depigmenting agents. In this work, in vitro and in silico techniques were employed to identify novel tyrosinase inhibitors from a set of 12 anilino-1,4-naphthoquinone derivatives. Results from the mushroom tyrosinase activity assay indicated that, among the 12 derivatives, three compounds (1, 5, and 10) demonstrated the most significant inhibitory activity against mushroom tyrosinase, surpassing the effectiveness of the kojic acid. Molecular docking revealed that all studied derivatives interacted with copper ions and amino acid residues at the enzyme active site. Molecular dynamics simulations provided insights into the stability of enzyme–inhibitor complexes, in which compounds 1, 5, and particularly 10 displayed greater stability, atomic contacts, and structural compactness than kojic acid. Drug likeness prediction further strengthens the potential of anilino-1,4-naphthoquinones as promising candidates for the development of novel tyrosinase inhibitors for the treatment of hyperpigmentation disorders.
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issn 1475-6366
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language English
publishDate 2024-12-01
publisher Taylor & Francis Group
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series Journal of Enzyme Inhibition and Medicinal Chemistry
spelling doaj-art-d0ec918f5481445ba291035eee6d50d22025-08-20T02:40:33ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2357174Anilino-1,4-naphthoquinones as potent mushroom tyrosinase inhibitors: in vitro and in silico studiesSahachai Sabuakham0Sutita Nasoontorn1Napat Kongtaworn2Thanyada Rungrotmongkol3Atit Silsirivanit4Ratchanok Pingaew5Panupong Mahalapbutr6Department of Biochemistry, Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Biochemistry, Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandProgram in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, ThailandProgram in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, ThailandDepartment of Biochemistry, Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, ThailandDepartment of Biochemistry, Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandTyrosinase, a pivotal enzyme in melanin synthesis, is a primary target for the development of depigmenting agents. In this work, in vitro and in silico techniques were employed to identify novel tyrosinase inhibitors from a set of 12 anilino-1,4-naphthoquinone derivatives. Results from the mushroom tyrosinase activity assay indicated that, among the 12 derivatives, three compounds (1, 5, and 10) demonstrated the most significant inhibitory activity against mushroom tyrosinase, surpassing the effectiveness of the kojic acid. Molecular docking revealed that all studied derivatives interacted with copper ions and amino acid residues at the enzyme active site. Molecular dynamics simulations provided insights into the stability of enzyme–inhibitor complexes, in which compounds 1, 5, and particularly 10 displayed greater stability, atomic contacts, and structural compactness than kojic acid. Drug likeness prediction further strengthens the potential of anilino-1,4-naphthoquinones as promising candidates for the development of novel tyrosinase inhibitors for the treatment of hyperpigmentation disorders.https://www.tandfonline.com/doi/10.1080/14756366.2024.2357174Tyrosinase inhibitionanilino-14-naphthoquinonesmolecular dockingmolecular dynamics simulations
spellingShingle Sahachai Sabuakham
Sutita Nasoontorn
Napat Kongtaworn
Thanyada Rungrotmongkol
Atit Silsirivanit
Ratchanok Pingaew
Panupong Mahalapbutr
Anilino-1,4-naphthoquinones as potent mushroom tyrosinase inhibitors: in vitro and in silico studies
Journal of Enzyme Inhibition and Medicinal Chemistry
Tyrosinase inhibition
anilino-14-naphthoquinones
molecular docking
molecular dynamics simulations
title Anilino-1,4-naphthoquinones as potent mushroom tyrosinase inhibitors: in vitro and in silico studies
title_full Anilino-1,4-naphthoquinones as potent mushroom tyrosinase inhibitors: in vitro and in silico studies
title_fullStr Anilino-1,4-naphthoquinones as potent mushroom tyrosinase inhibitors: in vitro and in silico studies
title_full_unstemmed Anilino-1,4-naphthoquinones as potent mushroom tyrosinase inhibitors: in vitro and in silico studies
title_short Anilino-1,4-naphthoquinones as potent mushroom tyrosinase inhibitors: in vitro and in silico studies
title_sort anilino 1 4 naphthoquinones as potent mushroom tyrosinase inhibitors in vitro and in silico studies
topic Tyrosinase inhibition
anilino-14-naphthoquinones
molecular docking
molecular dynamics simulations
url https://www.tandfonline.com/doi/10.1080/14756366.2024.2357174
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