8-异戊基取代的黄酮类化合物的合成及其抑制MDA-MB-231细胞增殖的活性评价

Synthesis of 8-Pentanyl Favonoids and Evaluation of Their Inhibition against MDA-MB-231 Cell Proliferation

以3,5-二甲氧基苯酚为起始原料，经5～6步反应，合成了8-异戊基取代的8个桑皮素类似物，经体外对人乳腺癌细胞MDA—MB．231增殖的抑制作用测试．结果显示：相对于槲皮素（IC5069．3μmol／L），桑皮素具有较大的抑制活性（IC5022．5μmol／L）；将桑皮素分子结构中的稠合环醚打开，即在8位引入异戊基、且对酚羟基甲醚化可进一步提高活性（IC5012．1μmol／L）；在3位上分别引入不同大小的疏水性基团（氢、苄基、烯丙基和异戊烯基）可保持高活性；5位引入疏水性基团可能是有利的；B环对位的甲氧基对活性影响显著；最高活性化合物7g的IC50值达到8．26gmol／L．

Starting from 3,5-dimethoxyphenol, eight morusin analogues bearing iso-pentanyl at the C-8 position have been synthesized through 5-6 steps, and their inhibitory activities against MDA-MB-231 cell proliferation have been evaluated in vitro. The tested results indicated： （1） morusin displayed more potent activity than quercetin （IC50：22.5 μmol/L vs 69.3 μmol/L）; （2） the activity could be increased （IC50：12.1 μmol/L） if the cycloolefin ether in morusin was disconnected, namely, iso-pentanyl was installed at the C-8 position, and all the phenolic hydroxyl groups were methoxylated; （3） the potent activity could be retained when the substituent at C-3 position was replaced by the different bulky hydrophobic groups （H, Bn, allyl and prenyl）, respectively; （4） the introduction of the hydrophobic groups to the C-5 position might be favorable to the inhibitory activity; （5） the para methoxy group at B cycle in the flavonoid seemed to have an important effect on the activity; （6） finally, the most potent compound was 7g with IC50 value of 8.26 μmol/L,