Lopes Thiago Inácio Barros, Coelho Roberta Gomes, Honda Neli Kika
Instituto de Química, Universidade Federal de Mato Grosso do Sul.
Instituto Federal de Educação Ciência e Tecnologia de Mato Grosso do Sul.
Chem Pharm Bull (Tokyo). 2018;66(1):61-64. doi: 10.1248/cpb.c17-00502.
Several applications have been proposed for tyrosinase inhibitors in the pharmaceutical, food bioprocessing, and environmental industries. However, only a few compounds are known to serve as effective tyrosinase inhibitors. This study evaluated the tyrosinase-related activity of resorcinol (1), orcinol (2) lecanoric acid (3), and derivatives of this acid (4-15). Subjected to alcoholysis, lecanoric acid (3), a depside isolated from the lichen Parmotrema tinctorum, produces orsellinic acid (2,4-dihydroxy-6-methylbenzoic acid) (4) and orsellinates (2,4-dihydroxy-6-methyl benzoates) (5-15). At 0.50 mM, methyl (5), ethyl (6), n-propyl (7), tert-butyl (11), and n-cetyl orsellinates (15) acted as tyrosinase activators, whereas n-butyl (8), iso-propyl (9), sec-butyl (10), n-pentyl (12), n-hexyl (13), and n-octyl orsellinates (14) behaved as inhibitors. Tyrosinase inhibition rose with chain elongation-n-butyl (8)<n-pentyl (12)<n-hexyl (13)<n-octyl orsellinates (14)-suggesting that the enzyme site can accept an eight-carbon alkyl chain. A kinetic study of n-octyl orsellinate (14) revealed uncompetitive inhibition of tyrosinase, with an inhibition constant of 0.99 mM.
酪氨酸酶抑制剂在制药、食品生物加工和环境工业领域已有多项应用被提出。然而，已知只有少数化合物可作为有效的酪氨酸酶抑制剂。本研究评估了间苯二酚（1）、苔色酸（2）、黑茶渍素（3）及其衍生物（4 - 15）与酪氨酸酶相关的活性。黑茶渍素（3）是从地衣染料衣中分离出的缩酚酸，经过醇解后可生成苔色酸（2,4 - 二羟基 - 6 - 甲基苯甲酸）（4）和苔色酸酯（2,4 - 二羟基 - 6 - 甲基苯甲酸酯）（5 - 15）。在0.50 mM浓度下，甲基苔色酸酯（5）、乙基苔色酸酯（6）、正丙基苔色酸酯（7）、叔丁基苔色酸酯（11）和正十六烷基苔色酸酯（15）表现为酪氨酸酶激活剂，而正丁基苔色酸酯（8）、异丙基苔色酸酯（9）、仲丁基苔色酸酯（10）、正戊基苔色酸酯（12）、正己基苔色酸酯（13）和正辛基苔色酸酯（14）则表现为抑制剂。酪氨酸酶抑制作用随链长增加而增强——正丁基苔色酸酯（8）<正戊基苔色酸酯（12）<正己基苔色酸酯（13）<正辛基苔色酸酯（14）——这表明酶位点能够接受一个八碳烷基链。对正辛基苔色酸酯（14）的动力学研究显示其对酪氨酸酶具有非竞争性抑制作用，抑制常数为0.99 mM。
