TYR and melanoma: In summary, the present work describes a low-cost drug discovery research for the synthesis of the first calixarene-based cluster (cyclic tetramer in chaliced shape) of arbutin as a novel water-soluble melanogenesis inhibitor with improved anti-tyrosinase (6-fold) effect and amplified melanoma inhibitory (27-fold) activity in comparison to its phenolic monomer, as reference drug.