1. Inhibition of tyrosinase by 4H-chromene analogs: Synthesis, kinetic studies, and computational analysis
- Author
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Edikarlos Brasil, José Rogério A. Silva, José Luiz Martins do Nascimento, Cláudio Nahum Alves, Barbarella de Matos Macchi, Paul V. Bernhardt, Erica de Tássia Carvalho Cardoso, Craig M. Williams, Luciana Morais Canavieira, Vera Lucia Eifler-Lima, Edilene O. Silva, Dharmarajan Sriram, and Jerônimo Lameira
- Subjects
0301 basic medicine ,Models, Molecular ,Molecular model ,Stereochemistry ,Tyrosinase ,Kinetics ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,Benzopyrans ,Binding site ,Enzyme Inhibitors ,Catechol oxidase ,Pharmacology ,chemistry.chemical_classification ,biology ,010405 organic chemistry ,Monophenol Monooxygenase ,Organic Chemistry ,Active site ,0104 chemical sciences ,030104 developmental biology ,Enzyme ,chemistry ,Pyrones ,biology.protein ,Molecular Medicine ,Kojic acid ,Agaricales - Abstract
Inhibition of mushroom tyrosinase was observed with synthetic dihydropyrano[3,2-b]chromenediones. Among them, DHPC04 displayed the most potent tyrosinase inhibitory activity with a Ki value of 4μM, comparable to the reference standard inhibitor kojic acid. A kinetic study suggested that these synthetic heterocyclic compounds behave as competitive inhibitors for the L-DOPA binding site of the enzyme. Furthermore, molecular modeling provided important insight into the mechanism of binding interactions with the tyrosinase copper active site.
- Published
- 2016