In the recent years we have developed aurones as a new class of TYR effectors. Aurones are naturally occurring flavonoids with a promising medicinal potential. They provide bright yellow flower pigmentation to some of the most advanced taxa in the plant kingdom, among other still little-known roles. Some derivatives from this subclass were found initially as melanogenesis suppressors in cell-based assays. A broader study showed that aurone analogues can actually adopt versatile behaviors, acting either as inhibitors, activators or alternative substrates of several isolated mushroom and bacterial TYRs, depending on their substitution pattern at the B-ring. In addition, we showed recently that the aurone scaffold is particularly suited for building interactions with active site residues located relatively far from the dicopper center in hsTYR, yielding compound 1 as one of the best hsTYR inhibitors reported to date (Ki = 0.35 µM), but with membrane penetration and water solubility issues probably due to the presence of a 2-hydroxypyridine-N-oxide (HOPNO) moiety. Thus, we propose to dismiss the HOPNO chelating group. In our previous studies, aurones bearing a resorcinol moiety, i.e.