Institute of Pharmacy, Chair of Pharmaceutical Biology, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.
Eur J Med Chem. 2010 Jun;45(6):2206-13. doi: 10.1016/j.ejmech.2010.01.060. Epub 2010 Jan 29.
Besides 2',4'-dihydroxy-4,6'-dimethoxy-3'-prenylchalcone (1) and 4-acetoxy-2',4'-dihydroxy-6'-methoxy-3'-prenylchalkon (2), both phase II metabolites of xanthohumol in rats, also a principally new chalcone 3'-coumaroyl-2',4,4'-trihydroxy-6'-methoxychalcone (3), structurally derived from helichrysetin (4) by introducing a second coumaroyl substructure at C-3' was synthesized. Furthermore new chalcones were synthesized by combination of the B-Ring fragments of helichrysetin, xanthohumol, xanthohumol C and xanthohumol H with ferulic or caffeic acid moieties in Ring A. Compound 3 showed the highest cytotoxic activity against HeLa cells with an IC50 value of 7.3+/-0.4 microM. Anti-oxidative effects were determined in the ORAC assay and revealed very strong activity for 3 and 3-methoxyhelichrysetin (6) exhibiting 7.7+/-0.3 and 6.0+/-1.3 Trolox equivalents, respectively. The anti-inflammatory activity of all compounds was measured in an in vitro ICAM-1 assay with human microvascular endothelial cells (HMEC-1) and compared with the activity of other structurally related chalcones. The results showed increasing anti-inflammatory activity for the new synthetic chalcones exhibiting a caffeoyl substructure with 3-hydroxyhelichrysetin (5) and 3-hydroxyxanthohumol H (14) being the most active. At 10 microM the TNFalpha induced expression of ICAM-1 was significantly reduced to 65.8 and 69.6% of control, respectively.
除了 2',4'-二羟基-4,6'-二甲氧基-3'-prenylchalcone（1）和 4-乙酰氧基-2',4'-二羟基-6'-甲氧基-3'-prenylchalkon（2），这两种都是黄烷酮在大鼠体内的 II 期代谢物，还合成了一种主要的新查耳酮 3'-香豆酰基-2',4,4'-三羟基-6'-甲氧基查耳酮（3），其结构是通过在 C-3' 处引入第二个香豆酰结构衍生自啤酒花黄素（4）。此外，通过将啤酒花黄素、黄烷酮、黄烷酮 C 和黄烷酮 H 的 B 环片段与 A 环中的阿魏酸或咖啡酸部分组合，合成了新的查耳酮。化合物 3 对 HeLa 细胞表现出最高的细胞毒性活性，IC50 值为 7.3+/-0.4 microM。在 ORAC 测定中测定了抗氧化作用，结果表明 3 和 3-甲氧基啤酒花黄素（6）具有非常强的活性，分别表现出 7.7+/-0.3 和 6.0+/-1.3 Trolox 当量。所有化合物的抗炎活性均在人微血管内皮细胞（HMEC-1）的体外 ICAM-1 测定中进行测量，并与其他结构相关的查耳酮的活性进行了比较。结果表明，具有 3-羟基啤酒花黄素（5）和 3-羟基黄烷酮 H（14）的新型合成查耳酮的抗炎活性逐渐增强，它们是最有效的。在 10 microM 时，TNFalpha 诱导的 ICAM-1 表达分别显著降低至对照的 65.8%和 69.6%。
