School of Food Science and Biotechnology (BK21 Plus), Kyungpook National University, Daegu 41566, Korea.
System Toxicology Research Center, Korea Institute of Toxicology, Daejeon 34114, Korea.
Int J Mol Sci. 2018 Apr 3;19(4):1067. doi: 10.3390/ijms19041067.
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 (1,3,5)-1,6-(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 , , and effectively decreased melanogenesis induced by α-melanocyte-stimulating hormone. In particular, compound 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 may be used as an anti-melanogenic agent for cosmetic purpose.
本研究旨在评估 1,6-二苯基-1,3,5-己三烯及其衍生物在 B16F10 小鼠黑色素瘤细胞和斑马鱼胚胎中的抗黑色素生成活性。合成了 25 种（1,3,5）-1,6-（取代苯基）己-1,3,5-三烯类似物，并使用三维定量构效关系方法预测分析了它们的非细胞毒性作用。通过评估 B16F10 细胞中黑色素含量和黑色素生成调节酶的表达，确定这些合成化合物对黑色素合成的抑制活性。通过观察用这些化合物处理的斑马鱼的身体色素沉着来验证抗黑色素生成活性。化合物 、 和 有效抑制了 α-促黑色素细胞激素诱导的黑色素生成。特别是，化合物 显著降低了 B16F10 细胞中小眼畸形相关转录因子（MITF）、酪氨酸酶（TYR）、酪氨酸酶相关蛋白 1（TYRP1）和 TYRP2 的 mRNA 和蛋白表达水平，并显著减少了斑马鱼发育幼虫的皮肤色素沉着。这些发现表明，化合物 可作为一种用于美容目的的抗黑色素生成剂。
