Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
Appl Biochem Biotechnol. 2012 Nov;168(6):1416-33. doi: 10.1007/s12010-012-9867-5. Epub 2012 Sep 12.
We describe the design, synthesis, and biological activities of 5-chloro-2-(substituted phenyl)benzo[d]thiazole derivatives as novel tyrosinase inhibitors. Among them, 4-(5-chloro-2,3-dihydrobenzo[d]thiazol-2-yl)-2,6-dimethoxyphenol (MHY884) and 2-bromo-4-(5-chloro-benzo[d]thiazol-2-yl)phenol (MHY966) showed inhibitory activity higher than or similar to kojic acid, against mushroom tyrosinase. Therefore, we carried out kinetic studies on the two compounds with potent tyrosinase inhibitory effects. Kinetic analysis of tyrosinase inhibition revealed that all of these compounds are competitive inhibitors. MHY884 and MHY966 effectively inhibited tyrosinase activity and reduced melanin levels in B16 cells treated with α-melanocyte stimulating hormone (α-MSH). These data strongly suggest that the newly synthesized compounds MHY884 and MHY966 could suppress production of melanin via inhibition of tyrosinase activity.
我们描述了 5-氯-2-（取代苯基）苯并[d]噻唑衍生物作为新型酪氨酸酶抑制剂的设计、合成和生物活性。其中，4-（5-氯-2,3-二氢苯并[d]噻唑-2-基）-2,6-二甲氧基苯酚（MHY884）和 2-溴-4-（5-氯-苯并[d]噻唑-2-基）苯酚（MHY966）对蘑菇酪氨酸酶的抑制活性高于或与曲酸相当。因此，我们对具有强酪氨酸酶抑制作用的两种化合物进行了动力学研究。酪氨酸酶抑制的动力学分析表明，所有这些化合物都是竞争性抑制剂。MHY884 和 MHY966 有效抑制了α-黑色素细胞刺激素（α-MSH）处理的 B16 细胞中的酪氨酸酶活性和黑色素水平。这些数据强烈表明，新合成的化合物 MHY884 和 MHY966 可以通过抑制酪氨酸酶活性来抑制黑色素的生成。
