合成新穎麴酸希夫鹼衍生物及其作為酪胺酸酶抑制劑之生物評估

Synthesis and Biological Evaluation of the Novel Kojic Acid-Schiff Base Derivative as Tyrosinase Inhibitor

吳鈺慈(Yu-Tzu Wu) ； 廖若湘(Ruo-Xiang Liao) ； 楊哿忻(Ke-Xin Yang) ； 陳明仁(Ming-Jen Chen)

《弘光學報》 90期 (2022/09) Pp. 65-74

https://doi.org/10.6615/HAR.202209_(90).0005

摘要

擁有亮白的肌膚一直是愛美女性追求的目標，在化妝品的市場中，對於美白產品的需求是逐年成長，因此新的美白成分與產品不斷地被開發出來。酪胺酸酶是黑色素形成的關鍵酵素，美白成分透過抑制酪胺酸酶活性來減少黑色素的生成量。麴酸在化妝品中常用來做為美白成分，能透過螯合酪胺酸酶活性中心的銅離子來抑制酪胺酸酶的活性。許多已知的酪胺酸酶抑制劑結構常含有希夫鹼架構，而這些結構中的硫與氮原子在螯合酪胺酸酶中的銅離子上扮演了關鍵的角色。本研究設計合成出具有巰基三唑希夫鹼架構的（Z）-5-羥基-2-｛［5-［（2-羥基-4-甲氧基苯亞甲基）胺基-1H-1,2,4-三氮唑-3-基］硫基］甲基｝-4H-喃-4-酮（I），將此化合物進行相關生物活性試驗評估，在抑制蘑菇酪胺酸酶活性部分，此衍生物的IC_(50)值為6.62 μM，麴酸為正向對照組（IC_(50) = 75.50 μM。酵素動力學實驗的結果顯示此化合物為非競爭型抑制劑。螯合銅離子能力結果顯示麴酸希夫鹼衍生物之螯合銅離子能力比對照組－麴酸來得好。CDOCKER理論計算結果顯示，麴酸希夫鹼衍生物與酪胺酸酶交互作用的能量低於麴酸。以上實驗結果證實此化合物具有開發成美白成分的潛力。

關鍵字

麴酸 ； 希夫鹼 ； 酪胺酸酶抑制劑 ； 美白

並列摘要

Owning bright white skin has always been the goal of beauty-loving women. In the cosmetic market, the demand for skin whitening products is growing year by year. Therefore, novel skin lightening ingredients and products were investigated constantly in recent years. Tyrosinase is the key emzyme in melanin synthesis and active ingredients decrease melanin content by inhibiting tyrosinase activities. Kojic acid was commonly used in cosmetic product as a whitening ingredient by chelating copper ions in the active site of tyrosinase. Many tyrosinase inhibitors have been reported containing schiff base moieties. Sulfur and nitrogen atoms of those compounds played a key role in chelating the copper ions of tyrosinase. We designed and synthesized the kojic acid-schiff base derivative containing a mercaptotriazole moiety. This derivative was evaluated its bioactivities in different systems. In mushroom tyrosinase inhibitory, the IC_(50) values of this derivative and kojic acid are 6.62 and 75.50 μM, respectively. The result of enzyme kinetics study shows that the schiff base compound is a non-competitive inhibitor. This derivative displays the better chelating effect than kojic acid as positive control in the study of chelating capacity of copper ions. In silico molecular docking analysis, the negative CDOCKER interaction energy score (76.0790) of the kojic acid-schiff base derivative is better than the score (63.9159) of kojic acid. In brief, the kojic acid-schiff base derivative has the potential to be the whitening ingredient of skin care products in the future.

並列關鍵字

kojic acid ； tyrosinase inhibitor ； schiff base ； whitening

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