Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (7): 1551-1558.DOI: 10.6023/cjoc201501010 Previous Articles     Next Articles

Notes

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

涂浪a,b, 麻巧宁a, 寇鑫晖a, 孙萍b,c, 杨永华a, 雷新胜a   

  1. a 复旦大学药学院 上海 201203;
    b 江西中医药大学药学院 南昌 330004;
    c 江中药业股份有限公司 南昌 330096
  • 收稿日期:2015-01-12 修回日期:2015-03-03 出版日期:2015-07-25 发布日期:2015-03-09
  • 通讯作者: 孙萍, 雷新胜 E-mail:leixs@fudan.edu.cn;sp@jzjt.com
  • 基金资助:

    国家自然科学基金(No. 21472024)资助项目.

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

Tu Langa,b, Ma Qiaoninga, Kou Xinhuia, Sun Pingb,c, Yang Yonghuaa, Lei Xishenga   

  1. a School of Pharmacy, Fudan University, Shanghai 201203;
    b School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004;
    c Jiangzhong Pharmaceutical Co., Ltd, Nanchang 330096
  • Received:2015-01-12 Revised:2015-03-03 Online:2015-07-25 Published:2015-03-09
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21472024).

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.

Key words: quercetin, prenylflavonoids, morusin, synthesis, cytotoxity