Activators of melanogenesis

Melanin is a mixture of natural pigments that plays an important role in cell protection against UV-radiation induced damage. It is produced in the basal layer of the epidermis by specialised dendritic cells. The process of melanin synthesis is called melanogenesis, it is highly regulated and involves specific enzymes. This thesis presents an overview of the molecules mainly involved in the regulation of melanogenesis and a critical analysis of the article: “A Potent Activator of Melanogenesis Identified from Small‐Molecule Screening”. The main objective of this article was to identify novel molecules capable of regulating melanogenesis, starting from the synthesis of a targeted combinatorial library of small molecules. The latter were synthesized starting from 5 carboxylic acids and 15 amines, characterized by different functional groups, analogous to those found in known modulators of melanogenesis. The screening of the library was performed in the murine melanocytes cell line melan-a, and several of the compounds tested were identified as enhancers of melanin levels in these cells. Treatment of melanocytes with the most active compound, named “A7”, caused a dose-dependent increase in melanin production and changes in cell pigmentation and morphology. Further analysis showed that the treatment with A7 resulted in an enhanced activity of tyrosinase, the key enzyme involved in melanin biosynthesis as it catalyses the conversion of L-tyrosine to L-DOPA, with no relevant changes in the expression levels of the enzyme. These outcomes suggest that A7 could be a potent activator of melanogenesis in murine melanocytes, potentially acting as an up-regulator of the enzyme tyrosinase.