Experimental and theoretical approaches for the development of 4H-Chromene derivatives as inhibitors of tyrosinase

Tyrosinase (TYR) is a key enzyme that catalyzes the synthesis of melanin in plants, microorganisms and mammalian cells. Kojic acid (KA) is a well-known TYR inhibitor widely used as a popular cosmetic skin-lightening ingredient. However, KA is reported to have poor inhibitory activity against pigment...

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Bibliographic Details
Published in:	Molecular simulation Vol. 47; no. 9; pp. 762 - 770
Main Authors:	Canavieira, Luciana Morais, Brasil, Edikarlos Macedo, Silva, Thiago de Melo e, Borges, Rosivaldo dos Santos, Silva, José Rogério Araújo, Lameira, Jerônimo, Bernhardt, Paul V., Williams, Craig M., Alves, Cláudio Nahum
Format:	Journal Article
Language:	English
Published:	Abingdon Taylor & Francis 13-06-2021 Taylor & Francis Ltd
Subjects:	Binding sites Chemical synthesis Crystallography DPPH Heterocyclic compounds Inhibitors kojic acid Melanin metal-binding Microorganisms Molecular docking Radicals Scavenging Tyrosinase
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Summary:	Tyrosinase (TYR) is a key enzyme that catalyzes the synthesis of melanin in plants, microorganisms and mammalian cells. Kojic acid (KA) is a well-known TYR inhibitor widely used as a popular cosmetic skin-lightening ingredient. However, KA is reported to have poor inhibitory activity against pigmentation within intact melanocytes or in clinical assays. In this study, a series of dihydropyrano[3,2-b] chromenedione (DHPC) (1a, 2a, 3a, 4a, 5a, 6a and 7a) and 1,8-dioxooctahydroxanthene (DOHX) (1b, 2b, 3b and 4b) derivatives were evaluated using a DPPH radical-scavenging assay. These results showed that 7a exhibited the most potent radical-scavenging activity. Compound 7a was characterised by X-ray crystallographic studies. Molecular docking was carried out to shed light on the mode of action and types of interaction between the compounds and the target. A metal-binding study suggested that these synthetic heterocyclic compounds may behave as competitive inhibitors for the L-DOPA binding site of the TYR. Finally, molecular modeling provided important insight into the mechanism of binding interactions with the TYR copper active site.
ISSN:	0892-7022 1029-0435
DOI:	10.1080/08927022.2021.1926455