Design, synthesis, and biological evaluation of symmetrical azine derivatives as novel tyrosinase inhibitors

Abstract

Abstract A series of symmetrical azine derivatives containing different substituted benzyl moieties were designed, synthesized, and evaluated for their inhibitory activity against tyrosinase. The results showed that compounds 3e, 3f, 3h, 3i, 3j, and 3k possess effective tyrosinase inhibition with IC50 values ranging from 7.30 μM to 62.60 μM. Particularly, compounds 3f displayed around three-fold improvement in the potency (IC50 = 7.30 ± 1.15 μM) compared to that of kojic acid (IC50 = 20.24 ± 2.28 μM) as the positive control. Kinetic study of compound 3f confirmed uncompetitive inhibitory activity towards tyrosinase indicating that it can bind to enzyme–substrate complex. Next, molecular docking analysis was performed to study the interactions and binding mode of the most potent compound 3f in the tyrosinase active site. Besides, the cytotoxicity of 3f, as well as its potency to reduce the melanin content were also measured on invasive melanoma B16F10 cell line. Also, 3f exhibited above 82% cell viability in the A375 cell line at 10 µM. Consequently, compounds 3f could be introduced as a potent tyrosinase inhibitor that might be a promising candidate in the cosmetics, medicine, and food industry.

Keywords

• Melanin
• Azine derivatives
• Tyrosinase inhibitors
• Molecular docking