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

Chul Park,Jin Jang,Jong-Sang Kim,Woo-Keun Kim,Jisun Oh,Sangwoo Lee,Jungeun Kim

doi:10.3390/ijms19041067

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.

Highlights

Melanin is a dark pigment produced through melanogenesis, a natural phenomenon occurring by the action of tyrosinase in melanocytes [1]
Given that tyrosinase is the key enzyme in melanin synthesis that exclusively occurs in melanocytes, melanogenesis may be effectively inhibited by antagonizing the catalytic activity and/or biosynthesis of tyrosinase [5,6,7,8,9]
The present study examined the anti-melanogenic potential of novel synthetic compounds for cosmetic purpose

Summary

Introduction

Melanin is a dark pigment produced through melanogenesis, a natural phenomenon occurring by the action of tyrosinase in melanocytes [1]. Most commercially available skin-whitening agents are tyrosinase inhibitors [9,10,11] such as kojic acid [12], arbutin [13], hydroquinone [14], ellagic acid [15], and their derivatives. All of these have drawbacks, including carcinogenicity, chemical instability, and poor bioavailability [9,10]

Methods

Results

Conclusion