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 analogs 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.
Highlights
According to the World Cancer Report, skin cancer constitutes 30% of all newly diagnosed cancers in the world [1]
To give more reliable results and enhance the robustness of the methodology used for the prediction of the affinity of the ligands studied, we extended this methodology to two well-known inhibitors of this enzyme: kojic acid and tropolone, with errors calculated for both, ranging from −0.23 kcal·mol−1 to
The INH3 inhibitor showed the lowest affinity to A. bisporus Tyrosinase (AbTYR) enzyme (ΔG°bind,exp = −2.62 kcal·mol−1), experimentally it was not possible to identify the reason of this lower affinity; our Molecular Dynamics (MD) simulations revealed that this inhibitor tends to leave the enzyme catalytic site, what can justify its weak binding
Summary
According to the World Cancer Report, skin cancer constitutes 30% of all newly diagnosed cancers in the world [1]. A number of tyrosinase inhibitors have been discovered and majority of them consist of the a phenol structure or of metal chelating agents [23,24]. These compounds represent one of the most promising classes of tyrosinase inhibitors in terms of potency, as with Kojico Acid (KA). KA is a metabolite produced mainly by fungi belonging to aspergillus genera This natural product presents a wide range of pharmacological profile such as skin-whitening, antioxidant, anti-tirosinase and anti-tumor [23,24,25].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
