Jeong Seong Hun, Ryu Young Bae, Curtis-Long Marcus J, Ryu Hyung Won, Baek Yoon Su, Kang Jae Eun, Lee Woo Song, Park Ki Hun
Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture & Life Science, Graduate School of Gyeongsang National University, Jinju 660-701, Korea.
J Agric Food Chem. 2009 Feb 25;57(4):1195-203. doi: 10.1021/jf8033286.
Twelve polyphenols (1-12) possessing tyrosinase inhibitory properties were isolated from the methanol (95%) extract of Morus lhou. The isolated compounds consisted of four flavanones (1-4), four flavones (5-8), and four phenylbenzofuranes (9-12). Moracin derivative 12 proved to be new a compound which was fully characterized. Compounds 1-12 were evaluated for both monophenolase and diphenolase (the two steps catalyzed by tyrosinase) inhibition to identify the structural characteristics required for mushroom tyrosinase inhibition. We observed that all parent compounds (1, 5, and 9) possessing an unsubstituted resorcinol group were highly effective inhibitors of monophenolase activity (IC(50) values of 1.3, 1.2, and 7.4 microM). The potency of the inhibitors diminished with alkyl substitution on either the aromatic ring or the hydroxyl functions. Interestingly, flavone 5 was shown to possess only monophenolase inhibitory activity, but flavanone 1 and phenylbenzofuran 9 inhibited diphenolase as well as monophenolase significantly. The inhibitory mode of these species was also dependent upon the skeleton: phenylbenzofuran 9 manifested a simple competitive inhibition mode for monophenolase and diphenolase; on the other hand flavanone 1 (monophenolase, k(3) = 0.1966 min(-1) microM(-1), k(4) = 0.0082 min(-1), and K(i)(app) = 0.0468 microM; diphenolase, k(3) = 0.0014 min(-1) microM(-1), k(4) = 0.0013 min(-1), and K(i)(app) = 0.8996 microM) and flavone 5 both showed time-dependent inhibition against monophenolase. Compound 1 operated according to the simple reversible slow binding model whereas compound 5 operated under the enzyme isomerization model.
从鲁桑的95%甲醇提取物中分离出12种具有酪氨酸酶抑制活性的多酚类化合物（1-12）。分离得到的化合物包括4种黄烷酮（1-4）、4种黄酮（5-8）和4种苯基苯并呋喃（9-12）。桑色素衍生物12被证明是一种新化合物，并对其进行了全面表征。对化合物1-12进行了单酚酶和双酚酶（酪氨酸酶催化的两个步骤）抑制活性评估，以确定抑制蘑菇酪氨酸酶所需的结构特征。我们观察到，所有具有未取代间苯二酚基团的母体化合物（1、5和9）都是单酚酶活性的高效抑制剂（IC(50)值分别为1.3、1.2和7.4 microM）。抑制剂的效力随着芳环或羟基上的烷基取代而降低。有趣的是，黄酮5仅表现出单酚酶抑制活性，但黄烷酮1和苯基苯并呋喃9对双酚酶和单酚酶均有显著抑制作用。这些物质的抑制模式也取决于骨架：苯基苯并呋喃9对单酚酶和双酚酶表现出简单的竞争性抑制模式；另一方面，黄烷酮1（单酚酶，k(3)=0.1966 min(-1) microM(-1)，k(4)=0.0082 min(-1)，K(i)(app)=0.0468 microM；双酚酶，k(3)=0.0014 min(-1) microM(-1)，k(4)=0.0013 min(-1)，K(i)(app)=0.8996 microM）和黄酮5对单酚酶均表现出时间依赖性抑制。化合物1按照简单的可逆慢结合模型起作用，而化合物5按照酶异构化模型起作用。
