1,2,4-Triazole-derived oxime ether derivatives: Synthesis, characterization, in vitro tyrosinase inhibition properties and in silico studies

Abstract

In the present study, a series of novel oxime ether derivatives bearing a 1,2,4-triazole moiety were synthesized, and the inhibitory effects of these compounds on tyrosinase were investigated. As is widely recognized, tyrosinase is a key enzyme involved in the biosynthesis of melanin, the pigment responsible for the coloration of skin, hair, and eyes. It catalyzes the oxidation of phenols, such as tyrosine, into quinones, which subsequently polymerize to form melanin. In addition to its role in biological pigmentation, tyrosinase contributes to the browning of fruits and vegetables. Its activity is tightly regulated, with implications for conditions like albinism and melanoma. Tyrosinase inhibitors are of great interest for cosmetic and therapeutic applications, particularly in managing hyperpigmentation disorders. The study is comprised of four parts. In the first part of the study, novel oxime ether derivatives were synthesized, and their structures were elucidated through the application of various analytical techniques, including FT-IR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. In the second part of the study, a series of computational analyses including DFT calculations, molecular docking and molecular dynamics simulations were conducted to evaluate the inhibitory potential of the synthesized compounds against tyrosinase. In the subsequent part of the study, the inhibitory effects of the compounds on tyrosinase were examined in vitro. The outcomes of the in silico and in vitro investigations were then compared with those of the reference molecule, kojic acid. The findings demonstrated that some of the synthesized compounds exhibited comparable or enhanced tyrosinase inhibitory activity to that of kojic acid. In the final part of the study drug-likeness and ADME analyses were performed on the compounds and the results indicated that all the compounds were deemed to possess drug-like characteristics and substantial potential.