Melanin is a natural polymer pigment which provides skin photoprotection against ultraviolet radiation. An excessive synthesis of melanin leads to hyperpigmentation disorders. Tyrosinase catalyzes the rate limiting steps on melanogenesis. Therefore, tyrosinase inhibitors have potential applications in medicine and cosmetic fields. We carried out herein the screening of a family of cyclic Morita-Baylis-Hillman adducts (MBH) to find out their effects on tyrosinase activity and on melanogenesis in murine melanoma B16F10 cell line. Kinetic analysis of tyrosinase inhibition showed that compounds 1a (2-hydroxymethyl) cyclohex-2-enone) and 3f (diethyl (1-(6-oxocyclohex-1-en-1-yl) ethyl-phosphonate) were competitive inhibitors, whereas the compound 2b (6-oxocyclohex-1-en-1-yl) ethyl acetate) was a non-competitive one. Additionally we have found that (1a, 2b and 3f) compounds had a strong melanogenesis inhibition effect in isobutylmethylxanthine (IBMX)-treated murine melanoma B16F10 cells when tested at low and non cytotoxic dose (10-50 µM), by attenuating the melanin production, intracellular tyrosinase activity and tyrosinase expression. Thus, we suggest that these compounds could be used as effective skin-whitening agents.

中文翻译：

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B16F10黑色素瘤细胞系中一系列新的Morita-Baylis-Hillman加合物的抗黑色素生成潜力。

黑色素是一种天然聚合物颜料，可为皮肤提供紫外线防护。黑色素的过度合成会导致色素沉着过度。酪氨酸酶催化黑素生成的限速步骤。因此，酪氨酸酶抑制剂在医学和化妆品领域具有潜在的应用。我们在这里进行了一个循环的森田-贝利斯-希尔曼加合物（MBH）家族的筛选，以发现它们对酪氨酸酶活性和鼠黑色素瘤B16F10细胞系中黑色素生成的影响。酪氨酸酶抑制作用的动力学分析表明，化合物1a（2-羟甲基）环己-2-烯酮）和3f（二乙基（1-（6-氧代环己基-1-en-1-基）乙基）膦酸酯）是竞争性抑制剂，而化合物2b（6-氧代环己-1-烯-1-基）乙酸乙酯）是非竞争性化合物。此外，我们发现（1a，2b和3f）化合物在异丁基甲基黄嘌呤（IBMX）处理的鼠黑色素瘤B16F10细胞中以低和非细胞毒性剂量（10-50 µM）进行测试，通过减弱黑色素的产生，细胞内酪氨酸酶活性和酪氨酸酶的表达，具有很强的抑制黑色素生成的作用。因此，我们建议这些化合物可以用作有效的皮肤增白剂。