Tyrosinase inhibition is very important in controlling
melanin synthesis. If
melanin synthesis is not controlled in metabolism, an unwanted increase in
melanin synthesis occurs. As
melanin plays a role in the formation of skin color, its unusual levels cause some skin disorders such as pregnancy
scars, age spots, and especially
skin cancer (
melanoma). However, the
tyrosinase activity is also related to
Parkinson's disease and some
neurodegenerative diseases. For all these reasons, the medicinal as well as the cosmetic industries focus on research on
tyrosinase inhibitors for the treatment of skin disorders and some
neurodegenerative diseases. In this study, 32 new 1,2,4-triazole-(thio)semicarbazide hybrid molecules (6a-p and 7a-p) were synthesized, starting from 4-amino-1-pentyl-3-phenyl-1H-1,2,4-triazole-5(4H)-one. These compounds were evaluated for their inhibitory activity against mushroom
tyrosinase. The results indicated that 6h, 6m, 6n, and 6p exhibited the most effective inhibitory activity, with IC50 values of 0.00162 ± 0.0109, 0.00166 ± 0.0217, 0.00165 ± 0.019, and 0.00197 ± 0.0063 μM, respectively, compared with
kojic acid as the reference
drug (IC50 = 14.09 ± 0.02 μM). Also, molecular docking analyses were performed to suggest possible binding poses for the
ligands. As a result, derivatives 6h, 6m, 6n, and 6p can be used as promising
tyrosinase inhibitor candidates in the medicinal,
cosmetics, or food industries.