Biological Evaluation and Molecular Docking Study of Ferrociphenol as an Antimelanogenic Agent

Cutaneous hyperpigmentation disorders are associated with abnormal accumulation of melanin pigments, which can be treated using depigmenting agents. In the present study, we investigated the effect of ferrociphenol (Fc-diOH), an organometallic intermediate used in the synthesis of hydroxy-ferrocifen derivatives and previously reported as a tyrosinase inhibitor, on melanogenesis in B16F10 melanoma cells. Cell viability, melanin content, and tyrosinase activity assays demonstrated that treatment with Fc-diOH significantly reduced intracellular melanin levels and tyrosinase activity by 32% and 25%, respectively, in B16F10 cells at 25 nM without inducing significant cytoxicity. Furthermore, the antimelanogenesis activity of Fc-diOH was confirmed in vivo using zebrafish (Danio rerio) embryos. Fc-diOH treatment at concentrations of 0.5 and 2 μM significantly inhibited melanin production and tyrosinase activity in zebrafish embryos without affecting embryonic development or viability. In addition, molecular docking analysis demonstrates that the p-hydroxyphenyl groups of Fc-diOH make close contacts with the active site of a predicted human tyrosinase model, compared to arbutin and phenylthiourea. Taken together, these results strongly suggest that Fc-diOH decreases tyrosinase activity and thereby negatively regulates melanogenesis in both B16F10 cells and zebrafish embryos. Therefore, Fc-diOH represents a promising candidate as a depigmentation agent for the treatment of hyperpigmentation disorders.