Evaluation and Optimization of the Anti-Melanogenic Activity of 1-(2-Cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone Derivatives

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 7; p. 1372
• Main Authors: Kim, Byung-Hak, Hong, Soo-Nam, Ye, Sang-Kyu, Park, Jung-Youl
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.04.2019; MDPI
• Subjects: (E)-N-(4-(3-(2-(cyclohexylmethoxy)phenyl)-3-oxoprop-1-en-1-yl)phenyl)acetamide (chalcone 21-21); alpha-melanocyte stimulating hormone (α-MSH); Bioactive compounds; Biological activity; Biosynthesis; Cellular manufacture; chalcone; Chemical modification; Cyclic AMP response element-binding protein; Cytotoxicity; Dermatitis; Drug development; Kinases; Kojic acid; Lead compounds; Melanin; melanin biosynthesis; Microphthalmia-associated transcription factor; Optimization; Phosphorylation; Proteins; Skin cancer; Transcription; Tyrosinase; (E)-N-(4-(3-(2-(cyclohexylmethoxy)phenyl)-3-oxoprop-1-en-1-yl)phenyl)acetamide (chalcone 21-21); chalcone; melanin biosynthesis; alpha-melanocyte stimulating hormone (-MSH); tyrosinase
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24071372

The chemical modification and optimization of biologically active compounds are essential steps in the identification of promising lead compounds for drug development. We previously reported the anti-melanogenic activity of 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone (chalcone 21). In this study, we synthesized 21 derivatives of chalcone 21 and evaluated their anti-melanogenic activity in -MSH-induced B16F10 cells. ( )- -(4-(3-(2-(Cyclohexylmethoxy)phenyl)-3-oxoprop-1-en-1-yl)phenyl)acetamide (chalcone 21-21) exhibited the strongest inhibition of cellular melanin production, with an IC value of 0.54 M. It was more potent than chalcone 21 and the known anti-melanogenic agents kojic acid and arbutin, whose IC values were 4.9, 38.5, and 148.4 M, respectively. Chalcone 21-21 decreased the expression and activity of tyrosinase. It also decreased the expression of TRP1, TRP2 and MITF, the phosphorylation of CREB and ERK1/2, and the transcriptional activity of MITF and CRE. Our results demonstrate that chalcone-21-21 is an effective lead compound with anti-melanogenic activity.