Tripeptides conjugated with thiosemicarbazones: new inhibitors of tyrosinase for cosmeceutical use

Abstract

The development of skin-care products is recently growing. Cosmetic formulas containing active ingredients with proven efficacy, namely cosmeceuticals, are based on various compounds, including peptides. Different whitening agents featuring anti-tyrosinase activity have been applied in the cosmeceutical field. Despite their availability, their applicability is often limited due to several drawbacks including toxicity, lack of stability, and other factors. In this work, we present the inhibitory effect on diphenolase activity of thiosemicarbazone (TSC)-peptide conjugates. Tripeptides FFY, FWY, and FYY were conjugated with three TSCs bearing one or two aromatic rings via amide bond formation in a solid phase. Compounds were then examined as tyrosinase and melanogenesis inhibitors in murine melanoma B16F0 cell line, followed by the cytotoxicity assays of these cells. In silico investigations explained the differences in the activity, observed among tested compounds. Mushroom tyrosinase was inhibited by TSC1-conjugates at micromolar level, with IC₅₀ lower than this for kojic acid, a widely used reference compound. Up to now, this is the first report regarding thiosemicarbazones conjugated with tripeptides, synthesised for the purpose of tyrosinase inhibition.

Graphical abstract

Keywords:

• Tyrosinase
• thiosemicarbazones
• peptide conjugates
• cosmeceuticals melanogenesis

Acknowledgements

The authors declare the support from the Polish Ministry of Science and Higher Education for the Faculty of Chemistry of Wroclaw University of Science and Technology, from the University of Florence, and from Polish National Agency for Academic Exchange (the Iwanowska Programme Scholarship for KH, agreement no. PPN/IWA/2019/1/00116/U/00001).

PL is the participant of “BioTechNan” project – Interdisciplinary Environmental Doctoral Studies KNOW in the field of Biotechnology and Nanotechnology, co-financed by the European Union. The PhD of PL is performed in the context of a doctorate between the PhD Schools in Drug Research and Innovative Treatments of the University of Florence (XXXV Ciclo) and in Chemical Sciences of the Wroclaw University of Science and Technology (Supervisors: PR and RL).

We kindly acknowledge the Erasmus + Programme for Traineeship at the Faculty of Chemistry of Wroclaw University of Science and Technology (September-December 2022) for MSc thesis of GC, co-tutored by RL and PR.

The molecular modelling was carried out using hardware and software resources of The Supercomputing and Networking Centre in Wroclaw (grant no. 197).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Polish National Agency for Academic Exchange (the Iwanowska Programme Scholarship for KH) under Grant P P N/IWA/2019/1/00116/U/00001; and Ministry of Education and Science as part of statutory subsidies for the Faculty of Chemistry of the Wrocław University of Technology under Grant 8211104160/9930160000.