Combined Kinetic Studies and Computational Analysis on Kojic Acid Analogs as Tyrosinase Inhibitors
Carlyle Ribeiro Lima,
José Rogério A. Silva,
Érica de Tássia Carvalho Cardoso,
Edilene O. Silva,
Jerônimo Lameira,
José Luiz Martins do Nascimento,
Davi do Socorro Barros Brasil,
Cláudio N. Alves
Affiliations
Carlyle Ribeiro Lima
Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil
José Rogério A. Silva
Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil
Érica de Tássia Carvalho Cardoso
Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil
Edilene O. Silva
Laboratório de Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil
Jerônimo Lameira
Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil
José Luiz Martins do Nascimento
Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil
Davi do Socorro Barros Brasil
Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil
Cláudio N. Alves
Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil
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.
