Validation of lichen derivatives as pro-pigmenting skin compounds – PIGMELICH

Synthesis of enatiopur lichenics derivatives is a 6 or 7 steps method depending on the derivative with a total yield of 15 to 20%. All compounds are each time tested on B16 cells (murine melanoma cells) in order to determine toxicity and melanin production. Once molecules are validated on cell assays, they are tested on mice skin explants. An electronic microscopy analysis is done to observe if a caracteristic phenotype is obtained after molecules incubation. The transcripts of the genes of interest are then quantified to confirm signaling pathways.

Several derivatives have been synthetized in order to determine the best stereochemical configuration leading to a pigmentation increase. The compounds increase melanin production by 20% in non stimulated B16 cells. Interestingly, not only the R or L enantiomer but the length of the carbonic chain play an important role. So we observe a depigmentation of 20% when the carbonic chain is shorter.

The objective of this project is to deeply characterize the molecular mechanism of these natural compounds. Understanding by which mean they can modulate skin pigmentation will allow to propose them as potential therapeutic and cosmetic tools.

- Patent extension: PCT 04/03/2011
- 18/04/2012: 2nd Patent: US201314395169 20130418
- November 2013: publication in preparation

Pigmentation of the skin is the most important body hallmarks with tremendous social issues. Pigmentation disorders like vitiligo is one of the most psychological devastating disease. Also, throughout history tanning has gone in and out fashion and in now central in our civilization. Because solar exposure induces skin cancer, fake products have been developed and the sunless tanner market is one of the most promising. For those medical and cosmetics reasons the identification of new original compounds promoting melanin synthesis in combination with sun-safety is crucial and a challenging task.
Lichens are evolutionary conserved symbiotic organisms of fungi and algae. These poorly studied organisms develop and survive under harsh climate including UV-exposure. We made thus the hypothesis that these organisms developed tools to survive UV-rays with the synthesis of pro-pigmentant compounds. It is those that have been track by the PNSCM and RTO teams.
Original compounds have been identified with biological pro-pigmentant activity (FR 1051622 Patent). Now, to be attractive towards Pharmaceutical and Cosmetics companies we aim to characterize deeper the compounds, generate chemical derivative and validate le pro-pimentant effect.