Li Chang-Wei, Dong Hua-Jin, Cui Cheng-Bin
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Molecules. 2015 Jan 27;20(2):2034-60. doi: 10.3390/molecules20022034.
Twelve galloyl glucosides 1-12, showing diverse substitution patterns with two or three galloyl groups, were synthesized using commercially available, low-cost D-glucose and gallic acid as starting materials. Among them, three compounds, methyl 3,6-di-O-galloyl-α-D-glucopyranoside (9), ethyl 2,3-di-O-galloyl-α-D-glucopyranoside (11) and ethyl 2,3-di-O-galloyl-β-D-glucopyranoside (12), are new compounds and other six, 1,6-di-O-galloyl-β-D-glucopyranose (1), 1,4,6-tri-O-galloyl-β-D-glucopyranose (2), 1,2-di-O-galloyl-β-D-glucopyranose (3), 1,3-di-O-galloyl-β-D-glucopyranose (4), 1,2,3-tri-O-galloyl-α-D-glucopyranose (6) and methyl 3,4,6-tri-O-galloyl-α-D-glucopyranoside (10), were synthesized for the first time in the present study. In in vitro MTT assay, 1-12 inhibited human cancer K562, HL-60 and HeLa cells with inhibition rates ranging from 64.2% to 92.9% at 100 μg/mL, and their IC50 values were determined to be varied in 17.2-124.7 μM on the tested three human cancer cell lines. In addition, compounds 1-12 inhibited murine sarcoma S180 cells with inhibition rates ranging from 38.7% to 52.8% at 100 μg/mL in the in vitro MTT assay, and in vivo antitumor activity of 1 and 2 was also detected in murine sarcoma S180 tumor-bearing Kunming mice using taxol as positive control.
以市售低成本的D - 葡萄糖和没食子酸为起始原料，合成了12种具有不同取代模式（含两个或三个没食子酰基）的没食子酰葡萄糖1 - 12。其中，3,6 - 二 - O - 没食子酰基 - α - D - 吡喃葡萄糖苷甲酯（9）、2,3 - 二 - O - 没食子酰基 - α - D - 吡喃葡萄糖苷乙酯（11）和2,3 - 二 - O - 没食子酰基 - β - D - 吡喃葡萄糖苷乙酯（12）这三种化合物为新化合物，另外六种，即1,6 - 二 - O - 没食子酰基 - β - D - 吡喃葡萄糖（1）、1,4,6 - 三 - O - 没食子酰基 - β - D - 吡喃葡萄糖（2）、1,2 - 二 - O - 没食子酰基 - β - D - 吡喃葡萄糖（3）、1,3 - 二 - O - 没食子酰基 - β - D - 吡喃葡萄糖（4）、1,2,3 - 三 - O - 没食子酰基 - α - D - 吡喃葡萄糖（6）和3,4,6 - 三 - O - 没食子酰基 - α - D - 吡喃葡萄糖苷甲酯（10），是本研究首次合成。在体外MTT试验中，1 - 12对人癌细胞K562、HL - 60和HeLa细胞具有抑制作用，在100 μg/mL时抑制率为64.2%至92.9%，并且在测试的三种人癌细胞系上它们的IC50值在17.2 - 124.7 μM范围内变化。此外，在体外MTT试验中，化合物1 - 12在100 μg/mL时对小鼠肉瘤S180细胞的抑制率为38.7%至52.8%，并且以紫杉醇作为阳性对照，在荷小鼠肉瘤S180的昆明小鼠中还检测了1和2的体内抗肿瘤活性。
