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

doi:10.6023/cjoc201610023

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

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新型二芳基-β-内酰胺类微管蛋白聚集抑制剂的结构改造及肿瘤细胞增殖抑制活性研究

冯克昌, 梁玉茹, 周鹏飞, 刘明明, 王洋

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,E-mail:lmm@fudan.edu.cn;王洋,E-mail:wangyang@shmu.edu.cn E-mail:lmm@fudan.edu.cn;wangyang@shmu.edu.cn
基金资助:
国家自然科学基金（Nos.21472025，81302257）资助项目.

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

School of Pharmacy, Fudan University, Shanghai 201203

Received:2016-10-13 Revised:2016-11-25 Published:2016-11-29
Contact: 10.6023/cjoc201610023 E-mail:lmm@fudan.edu.cn;wangyang@shmu.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 21472025, 81302257).

1. Structural Modification and Inhibitory Activity on Tumor Cell Proliferation of Novel Diaryl-β-lactam Compounds as Tubulin Aggregation Inhibitors.PDF(30597KB)

Abstract

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

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Feng Kechang, Liang Yuru, Zhou Pengfei, Liu Mingming, Wang Yang. Structural Modification and Inhibitory Activity on Tumor Cell Proliferation of Novel Diaryl-β-lactam Compounds as Tubulin Aggregation Inhibitors[J]. Chin. J. Org. Chem., 2017, 37(3): 683-690.

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新型二芳基-β-内酰胺类微管蛋白聚集抑制剂的结构改造及肿瘤细胞增殖抑制活性研究

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

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