SYNTHESIS OF NOVEL BOLDINE AMIDES AND THEIR IN VITRO INHIBITORY EFFECTS ON A MUSHROOM TYROSINASE

Boldine ((S)-2,9-dihydroxy-1,10-dimethoxy-aporphine) has been defined as the major alkaloid in Chilean boldo tree. Besides its diverse pharmacological activities, e.g. neuroprotective, cytoprotective, anti-inflammatory activities, boldine also exhibits tyrosinase-inhibiting effect. Tyrosinase [EC 1.14.18.1] is well known as a bifunctional enzyme that is responsible for the melanin biosynthesis. Considering the diphenolic structural feature of the alkaloid, which is associated with its tyrosinase inhibitory properties, herein we first modified the boldine core and then linked it with the natural phenolic antioxidants such as: caffeic-, ferulic- and sinapic acids. Furthermore, the newly amides were tested in vitro on the mushroom tyrosinase. Our results indicated, that amongst the tested boldine derivatives, caffeoyl- and feruloylamides have shown the anti-tyrosinase activity closely correlated with a hydroquinone, used as a standard.