New tyrosinase-targeted compounds based on structural variants of the prototype unit 4-aminophenol have been synthesized and screened for their potential as antitumour agents against malignant melanoma. Cytotoxicity assays showed thatN-4-hydroxyphenylglycine (NHPG) and its α-methyl derivatives methylphenylglycine and dimethyl-phenylglycine exhibit significant antiproliferative effects on pigmented human melanoma cell lines (HBL), with inhibitory concentrations at 50% (IC50) around 80 μg/ml. A marked increase in cytotoxicity was observed with morpholine-containing 4-amino-phenols, e.g.N-(2-morpholinoethyl)-4-aminophenol, which showed an IC50of 20 μg/ml of HBL cells. Much more pronounced was the effect of the diacetoxy-derivative, DIAcMoAC, which showed an IC50of 15 μg/ml on HBL cells and as low as 2 μg/ml on tyrosinase-containing, non-pigmented human melanoma cells (LND1), with a toxicity response of the same order of magnitude as that of melphalan. These results open interesting perspectives in the design of new targeted pro-drugs against malignant melanoma.