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

Starting from 3,5-dimethoxyphenol, eight morusin analogues bearing iso-pentanyl at the C-8 position have been synthesized through 5 similar to 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 mu mol/L vs 69.3 mu mol/L); (2) the activity could be increased (IC50: 12.1 mu mol/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 mu mol/L.