Laboratório de Química Biológica, Departamento de Química Fundamental, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil.
Laboratório de Catálise Orgânica, Departamento de Química Fundamental, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil.
Int J Biol Macromol. 2019 Sep 1;136:1034-1041. doi: 10.1016/j.ijbiomac.2019.06.120. Epub 2019 Jun 21.
Many skin disorders and diseases are related to tyrosinase activity, in particular, due to the vital role played by this enzyme in the melanogenic process. Although numerous natural and synthetic tyrosinase inhibitors have been published, substantial efforts have been made to understand the influence of tyrosinase inhibition on the viability of melanoma cells. Here, we assess the impact of two keto-derivatives: 2-acetyl-furan (F1), furfural-acetone (F2), and two carboxyl-derivatives: 2-furan-acrylic acid (F3), 5-methyl-2-furan-acrylic acid (F4), on the mushroom tyrosinase (mTYR) activity, by applying spectroscopic, kinetic and theoretical techniques. From an exploratory and theoretical point of view, results indicated that albeit all furans bind tightly to and inhibit mTYR very efficient, carboxyl-furan derivatives presented best inhibitory activities than keto- derivatives and performed the inhibition competitively and reversible. Moreover, we examined the influence of carboxyl derivative on the viability of melanoma cells. Results expose differential toxicity of these furan derivatives, which indicates a piece of evidence that furan inhibition activity may be related to its toxicity against B16F10 cells.
许多皮肤疾病与酪氨酸酶活性有关，特别是由于该酶在黑色素生成过程中起着至关重要的作用。尽管已经发表了许多天然和合成的酪氨酸酶抑制剂，但人们仍在努力理解酪氨酸酶抑制对黑色素瘤细胞活力的影响。在这里，我们评估了两种酮衍生物：2-乙酰呋喃（F1）、糠醛-丙酮（F2）和两种羧酸衍生物：2-呋喃丙烯酸（F3）、5-甲基-2-呋喃丙烯酸（F4）对蘑菇酪氨酸酶（mTYR）活性的影响，应用了光谱、动力学和理论技术。从探索性和理论角度来看，结果表明，尽管所有呋喃都紧密结合并非常有效地抑制 mTYR，但羧酸呋喃衍生物的抑制活性优于酮衍生物，并且表现出竞争性和可逆性抑制。此外，我们研究了羧酸衍生物对黑色素瘤细胞活力的影响。结果揭示了这些呋喃衍生物的不同毒性，这表明一个证据，即呋喃抑制活性可能与其对 B16F10 细胞的毒性有关。
