title: Inhibition of tyrosinase by 4H-chromene analogs: Synthesis, kinetic studies, and computational analysis.
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 Kivalue of 4 μm, 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.
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, PA, Brazil.|School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Edikarlos M
authors.initials: EM
authors.lastname: Brasil
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Luciana M
authors.initials: LM
authors.lastname: Canavieira
authors.affiliation: Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Érica T C
authors.initials: ÉTC
authors.lastname: Cardoso
authors.affiliation: Laboratório de Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Edilene O
authors.initials: EO
authors.lastname: Silva
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, PA, Brazil.|Programa de Pós-Graduação em Química Medicinal, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Jerônimo
authors.initials: J
authors.lastname: Lameira
authors.affiliation: Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.|Programa de Pós-Graduação em Química Medicinal, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: José L M
authors.initials: JLM
authors.lastname: Nascimento
authors.affiliation: Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Eifler-Lima
authors.affiliation: Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.|Programa de Pós-Graduação em Química Medicinal, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Barbarella M
authors.initials: BM
authors.lastname: Macchi
authors.affiliation: Medicinal Chemistry and Antimycobacterial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science, Hyderabad, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Bernhardt
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: José Rogério Araújo
authors.initials: JRA
authors.lastname: Silva
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Williams
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, PA, Brazil.|Programa de Pós-Graduação em Química Medicinal, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Cláudio N
authors.identifier: http://orcid.org/0000-0001-6576-4229
authors.initials: CN
authors.lastname: Alves
mesh_terms: D000363:Agaricales / Q000187:drug effects / Q000201:enzymology*; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D001578:Benzopyrans; D004791:Enzyme Inhibitors; D011753:Pyrones; C011890:kojic acid; D014442:Monophenol Monooxygenase
keywords: inhibitor; kinetic assays; kojic acid; molecular modeling; multicomponent reaction; tyrosinase