Synthesis of Dimeric Cinnamoylamide Derivatives and Evaluation of Their Depigmenting Activities

Human skin color is primarily determined by melanin production. Melanin is a biopigment synthesized by melano-cytes in a specialized cellular organelle called the melano-some.1 Synthesized melanin is transferred from melanocytes to keratinocytes in the human epidermis. Melanin is located in the outer layer of the skin and protects against the harmful effects of ultraviolet (UV) irradiation. However, overproduc-tion of melanin and its abnormal accumulation in human skin causes a variety of cosmetic and clinical problems.2 Melanin synthesis is a complex process that involves enzy-matic and chemical reactions. Among the enzymes involved in melanin synthesis, tyrosinase is the most critical and rate limiting enzyme. Tyrosinase3 is a copper-containing enzyme that catalyzes two distinct reactions involved in melanin synthesis; the hydroxylation of L-tyrosine to L-dopa and th