Computational Simulation of Molecular Docking and Adme/Tox Analysis of Triazole-Based Kojic Acid Analogues

The enzyme Tyrosinase (TYR), a constituent of the biosynthetic steps of melanogenesis, is linked to various skin disorders in individuals. In particular, hyperpigmentation, melasma and skin cancer in the non-melanomic form and malignant melanoma stand out as some dyschromias caused by TYR kinetic changes. The vast majority of skin diseases are treated with substances containing depigmenting agents, which have demonstrated adverse effects on skin melanocytes, such as kojic acid (AK), which over the years has gained prominence in research into TYR inhibitors. As a result, TYR has become an important biological target for the development of new drugs. In this work, new TYR inhibitors were investigated, using AK analogues as a line of study, in this case, the 1,2,3-triazole analogues of AK, using the computational approaches of ADME/Tox, and molecular docking. ADME/Tox analyzes showed that AK triazole analogues exhibit drug-like properties, presenting no problematic warnings. Molecular docking calculations showed agreements with experimental data, with distances close to crystallography. All inhibitors presented distances close to 3.65 Å from the hydroxyl group of the AK part based on 1,2,3-triazole in relation to Cu2+, with conformations in line with the energy produced by AK in molecular redocking calculations, obtaining a r2 = 0.58 in linear regression with ∆G versus MOLDOCK scoring. Theoretical Chemistry methods allowed validation for studies related to new TYR inhibitors.