Novel (1E,3E,5E)-1,6-bis(Substituted phenyl)hexa-1,3,5-triene Analogs Inhibit Melanogenesis in B16F10 Cells and Zebrafish.

Abstract

The present study aimed to evaluate the anti-melanogenic activity of 1,6-diphenyl-1,3,5-hexatriene and its derivatives in B16F10 murine melanoma cells and zebrafish embryos. Twenty five (1E,3E,5E)-1,6-bis(substituted phenyl)hexa-1,3,5-triene analogs were synthesized and their non-cytotoxic effects were predictively analyzed using three-dimensional quantitative structure-activity relationship approach. Inhibitory activities of these synthetic compounds against melanin synthesis were determined by evaluating melanin content and melanogenic regulatory enzyme expression in B16F10 cells. The anti-melanogenic activity was verified by observing body pigmentation in zebrafishes treated with these compounds. Compound #2, #4, and #6 effectively decreased melanogenesis induced by α-melanocyte-stimulating hormone. In particular, compound #2 remarkably lowered the mRNA and protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and TYRP2 in B16F10 cells and substantially reduced skin pigmentation in the developed larvae of zebrafish. These findings suggest that compound #2 may be used as an anti-melanogenic agent for cosmetic purpose.

• Authors: Jisun Oh, Jungeun Kim, Jin Ho Jang, Sangwoo Lee, Chul Min Park, Woo-Keun Kim, Jong-Sang Kim
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 4 (Apr 03 2018) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 29614034 (Publication Type: Journal Article)

Chemical References

• Melanins
• Membrane Glycoproteins
• Microphthalmia-Associated Transcription Factor
• Diphenylhexatriene
• Melanocyte-Stimulating Hormones
• Oxidoreductases
• Tyrp1 protein, mouse
• Monophenol Monooxygenase
• Intramolecular Oxidoreductases
• dopachrome isomerase

Topics

• Animals
• Cell Line, Tumor
• Diphenylhexatriene (analogs & derivatives, pharmacology)
• Intramolecular Oxidoreductases (genetics, metabolism)
• Melanins (biosynthesis)
• Melanocyte-Stimulating Hormones (pharmacology)
• Melanocytes (drug effects, metabolism)
• Membrane Glycoproteins (genetics, metabolism)
• Mice
• Microphthalmia-Associated Transcription Factor (genetics, metabolism)
• Monophenol Monooxygenase (genetics, metabolism)
• Oxidoreductases (genetics, metabolism)
• Skin Pigmentation (drug effects)
• Zebrafish