Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (3): 683-690.DOI: 10.6023/cjoc201610023 Previous Articles     Next Articles



冯克昌, 梁玉茹, 周鹏飞, 刘明明, 王洋   

  1. 复旦大学药学院 上海 201203
  • 收稿日期:2016-10-13 修回日期:2016-11-25 发布日期:2016-11-29
  • 通讯作者: 刘明明,;王洋,;
  • 基金资助:


Structural Modification and Inhibitory Activity on Tumor Cell Proliferation of Novel Diaryl-β-lactam Compounds as Tubulin Aggregation Inhibitors

Feng Kechang, Liang Yuru, Zhou Pengfei, Liu Mingming, Wang Yang   

  1. School of Pharmacy, Fudan University, Shanghai 201203
  • Received:2016-10-13 Revised:2016-11-25 Published:2016-11-29
  • Contact: 10.6023/cjoc201610023;
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21472025, 81302257).

Our previous studies have found that diaryl-β-lactam derivative (S)-4-(3-hydroxy-4-methoxyphenyl)-3-methylene-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (3a) possesses potent antitumor activity and its mechanism of action was confirmed as a tubulin aggregation inhibitor. In this paper, 22 novel analogs were synthesized through modifications of the phenolic hydroxyl group in B ring of compound 3a. The structures of all target compounds were characterized by 1H NMR, 13C NMR and HRMS data. The inhibition against proliferation of A2780, MDA-MB-231, SKOV-3 and Hela cells were tested by thiazolyl blue tetrazolium bromide (MTT) assay, and the bioassay results demonstrated that most of these derivatives showed good anti-proliferative activities. Among them, (S)-1-(3,4,5-trimethoxyphenyl)-4-(3-(4-nitrobenzoyloxyl)-4-methoxyphenyl)-3-meth-ylene-azetidin-2-one (5n) exhibited most potent activities against the above four cancer cells with the corresponding IC50 values of 0.055, 0.105, 0.084 and 0.102 μmol/L, respectively, indicating that these type of compounds merit further investigation.

Key words: diaryl-β-lactam, tubulin aggregation inhibitor, antitumor