Discovery of small molecules that inhibit melanogenesis via regulation of tyrosinase expression

Abstract: 5,6,7,8-Tetrahydro-4H-cyclohepta[d]isoxazole derivatives were synthesized and evaluated as a novel class of inhibitors for α-melanocyte-stimulating hormone (α-MSH) induced melanogenesis in a mouse melanoma B16F10 cell line. Compound 8e (IC50 =0.67μM), 8h (IC50 =1.01μM) and 9b (IC50 =0.99μM) exhibited a potent inhibitory activity approximately 85- to 126-fold greater than kojic acid, a well-known potent inhibitor. A biochemical study indicates that the activity of this series should be displayed via down-regulation of the expression of tyrosinase. [Copyright &y& Elsevier]