Inhibition of tyrosinase activity and melanin production by the chalcone derivative 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone

Abstract

Abnormal accumulation of melanin pigments in the skin can be lead to hyperpigmentation disorders and melanoma. Melanin biosynthesis is ultimately regulated by the rate-limiting enzyme tyrosinase. In the present study, we synthesized chalcone derivatives and identified 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone (chalcone-21) as an anti-melanogenic substance in B16F10 melanoma cells. Chalcone-21 strongly inhibited cellular melanin production and tyrosinase activity in B16F10 melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH) or protoporphyrin IX. In addition, the compound suppressed not only the expression of tyrosinase, tyrosinase-related protein-1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF), but also the transcriptional activity of tyrosinase and MITF. Our results demonstrated chalcone-21 to be an effective depigmenting agent.

Keywords: 1-(2-Cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone (chalcone-21); Hyperpigmentation disorder; Melanin; Melanogenesis; Tyrosinase.