Depigmenting properties of
tyrosinase inhibitors (TAi) boosted the search for new compounds applicable in
cosmetics.
Kojic acid, a
3-hydroxy-4-pyrone, is the most studied
tyrosinase inhibitor but undesirable side effects, like
dermatitis, and unspecified mechanism led to its exclusion in several countries. To discover safer and more efficient TA, we evaluated
tyrosinase inhibitory effect of twelve 3-hydroxy-4-pyridinones (3,4-HPO) in vitro and considering the two reaction steps of inhibition in mushroom
tyrosinase enzyme. In parallel we performed molecular docking studies in human and mushroom
enzymes.
Ligands I6 and I11 were the most effective compounds considering their inhibitory activity in both reaction steps. Our studies revealed that I6 has a non-competitive and mixed type of inhibition for
monophenolase and diphenolase activity, while
ligand I11 showed a mixed and competitive inhibition type for each reaction step. Molecular Docking results indicated that
ligands tend to bind the
enzyme by coordinating directly with the binuclear cooper centre and highlighted the relevance of voluminous and non-polar substituents at R2 to avoid the binding of the
ligands to the
enzyme. The work clarifies the type of inhibition established for
kojic acid and points out the differences found for the set of 3,4-HPO
chelators studied as prospective
tyrosinase inhibitors.