Biological evaluation and molecular docking study of Ferrociphenol as an anti-melanogenic agent

Abstract

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 for the synthesis of hydroxy-ferrocifen derivatives, which has previously been shown as an inhibitor of Sepia tyrosinase activity, on the inhibition of melanogenesis in B16F10 melanoma cells. Cell viability, melanin quantification and tyrosinase activity assay demonstrated that Fc-diOH treatment reduced the amount of intracellular melanin and tyrosinase activity by 32 and by 25%, respectively, in B16F10 melanoma cells at 25 nM without significant cellular toxicity. Furthermore, the biological activity of Fc-diOH against melanogenesis was confirmed in in vivo experiments using zebrafish Danio rerio embryos. We found that Fc-diOH inhibited melanin production and tyrosinase activity of zebrafish embryos treated with 0.5 and 2 {micro}M respectively, without affecting embryonic development or viability. In addition and interestingly, molecular docking analysis demonstrates that the p-hydroxyphenyl groups of Fc-diOH make close contacts with the active site of tyrosinase, compared to arbutin and phenylthiourea, which could be due to its structural homology with the tyrosinase substrate. Therefore, these results strongly suggest that Fc-diOH decreases tyrosinase activity, thereby negatively regulating melanogenesis in B16F10 cells and zebrafish embryos. Thus, Fc-diOH could be used as a depigmentation agent for the treatment of various hyper-pigmentation disorders.