Discovery of a Novel Cyclopeptide as Tyrosinase Inhibitor for Skin Lightening.

Abstract

Background: Melanin synthesis plays a crucial role in skin pigmentation, and inhibiting tyrosinase, the key enzyme in melanin production, is a primary strategy for developing skin-lightening agents. This study investigates the tyrosinase inhibitory potential of CHP-9, a novel cyclopeptide, and evaluates its cytotoxicity and efficacy as a cosmetic depigmenting agent.

Methods: CHP-9 was synthesized via a solid-phase peptide synthesis strategy. The tyrosinase inhibitory activity was assessed using an enzymatic assay, while its effects on melanin content were evaluated in cultured human melanocytes. The MTT assay was performed to assess cytotoxicity across a range of CHP-9 concentrations (0.0781-10 mg/mL). Molecular docking simulations were conducted to elucidate the interaction between CHP-9 and human tyrosinase (PDB ID: 5M8M). Statistical analysis was performed using GraphPad Prism Software, and significance was determined via one-way ANOVA.

Results: CHP-9 exhibited significant tyrosinase inhibition (28.57% at 1% concentration) and reduced melanin content in treated melanocytes from 30.90 ± 1.13 to 23.51 ± 1.14 µg/mL. Cytotoxicity assays confirmed CHP-9's high biocompatibility, with cell viability exceeding 90% at concentrations up to 2.5 mg/mL. Docking studies revealed strong binding affinity between CHP-9 and key tyrosinase residues via hydrogen bonding, supporting its inhibitory mechanism.

Conclusions: CHP-9 exhibited significant tyrosinase inhibition (28.57% at 1% concentration) and reduced melanin content in melanocytes, while maintaining over 90% cell viability at effective doses. These findings suggest that CHP-9 is a safe and effective candidate for cosmetic skin-lightening applications. Further research is needed to enhance formulation stability and evaluate long-term efficacy in vivo.