title: Combined kinetic studies and computational analysis on kojic acid analogous as tyrosinase inhibitors.
abstract: Tyrosinase is a key enzyme in melanin synthesis and widely distributed in plants and animals tissues. In mammals, this enzyme is related to pigment production, involved in wound healing, primary immune response and it can also contribute to catecholamines synthesis in the brain. Consequently, tyrosinase enzyme represents an attractive and selective target in the field of the medicine, cosmetics and bio-insecticides. In this paper, experimental kinetics and computational analysis were used to study the inhibition of tyrosinase by analogous of Kojic acid. The main interactions occurring between inhibitors-tyrosinase complexes and the influence of divalent cation (Cu2+) in enzymatic inhibition were investigated by using molecular docking, molecular dynamic simulations and electrostatic binding free energy by using the Linear Interaction Energy (LIE) method. The results showed that the electrostatic binding free energy are correlated with values of constant inhibition (r2 = 0.97).Thus, the model obtained here could contribute to future studies of this important system and, therefore, eventually facilitate development of tyrosinase inhibitors.
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil. carlylelima@hotmail.com.
authors.forename: Carlyle Ribeiro
authors.initials: CR
authors.lastname: Lima
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil. rogerio@ufpa.br.
authors.forename: José Rogério A
authors.initials: JR
authors.lastname: Silva
authors.affiliation: Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil. tassia.10@gmail.com.
authors.forename: Erica
authors.initials: E
authors.lastname: de Tássia Carvalho Cardoso
authors.affiliation: Laboratório de Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil. edilene@ufpa.br.
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, 66075-110 Belém, PA, Brazil. lameira@ufpa.br.
authors.forename: Jerônimo
authors.initials: J
authors.lastname: Lameira
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil. tassia.10@gmail.com.
authors.forename: José Luiz Martins
authors.initials: JL
authors.lastname: do Nascimento
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil. davibb@ufpa.br.
authors.forename: Davi
authors.initials: D
authors.lastname: do Socorro Barros Brasil
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil. nahum@ufpa.br.
authors.forename: Cláudio N
authors.initials: CN
authors.lastname: Alves
mesh_terms: D020134:Catalytic Domain; D007700:Kinetics; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011487:Protein Conformation; D011753:Pyrones / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D011753:Pyrones; C011890:kojic acid; D014442:Monophenol Monooxygenase