Anti-melanogenesis and anti-tyrosinase properties of aryl-substituted acetamides of phenoxy methyl triazole conjugated with thiosemicarbazide: Design, synthesis and biological evaluations

A series of aryl phenoxy methyl triazole conjugated with thiosemicarbazides were designed, synthesized, and evaluated for their tyrosinase inhibitory activities in the presence of L-dopa and L-tyrosine as substrates. All the compounds showed tyrosinase inhibition in the sub-micromolar concentration. Among the derivatives, compound 9j bearing benzyl displayed exceptionally high potency against tyrosinase with IC50 value of 0.11 mu M and 0.17 mu M in the presence of L-tyrosine and L-dopa as substrates which is significantly lower than that of kojic acid as the positive control with an IC50 value of 9.28 mu M for L-tyrosine and 9.30 mu M for L-dopa. According to Lineweaver-Burk plot, 9j demonstrated an uncompetitive type of inhibition in the kinetic assay. Also, in vitro antioxidant activities determined by DPPH assay recorded an IC50 value of 68.43 mu M for 9i. The melanin content of 9j was determined on B16F10 melanoma human cells which demonstrated a significant reduction of the melanin content. Moreover, the binding energies corresponding to the same ligand as well as computer-aided drug-likeness and pharmacokinetic studies were also carried out. Compound 9j also possessed metal chelation potential correlated to its high anti-TYR activity.

Automated summary

A series of novel compounds were designed, synthesized, and evaluated for their tyrosinase inhibitory activities, antioxidant activities, and melanin content reduction. Compound 9j showed significant anti-tyrosinase activity and reduction in melanin content.