Chen Zhiyong, Cai Dachuan, Mou Dehai, Yan Qin, Sun Yifeng, Pan Wenlong, Wan Yiqian, Song Huacan, Yi Wei
Guangdong Provincial Public Laboratory of Analysis and Testing Technology, China National Analytical Center (Guangzhou), Building 34, 100 Xianlie Middle Road, Guangzhou 510070, PR China.
School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
Bioorg Med Chem. 2014 Jul 1;22(13):3279-84. doi: 10.1016/j.bmc.2014.04.060. Epub 2014 May 15.
Here a new class of hydroxy- or methoxy-substituted 5-benzylidene(thio)barbiturates were designed, synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed that several compounds had more potent tyrosinase inhibitory activities than the widely used tyrosinase inhibitor kojic acid (IC50=18.25μM). In particular, 3',4'-dihydroxylated 1e was found to be the most potent inhibitor with IC50 value of 1.52μM. The inhibition mechanism analysis revealed that the potential compounds 1e and 2e exhibited such inhibitory effects on tyrosinase by acting as the irreversible inhibitors. Structure-activity relationships' (SARs) analysis also suggested that further development of such compounds might be of interest.
在此，设计、合成了一类新型的羟基或甲氧基取代的5-亚苄基（硫代）巴比妥酸盐，并评估了它们对蘑菇酪氨酸酶双酚酶活性的抑制作用。结果表明，几种化合物具有比广泛使用的酪氨酸酶抑制剂曲酸（IC50 = 18.25μM）更强的酪氨酸酶抑制活性。特别地，发现3'，4'-二羟基化的1e是最有效的抑制剂，IC50值为1.52μM。抑制机制分析表明，潜在化合物1e和2e通过作为不可逆抑制剂对酪氨酸酶表现出这种抑制作用。构效关系（SARs）分析还表明，这类化合物的进一步开发可能具有意义。
