Citation: 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]. Chinese Journal of Organic Chemistry, ;2017, 37(3): 683-690. doi: 10.6023/cjoc201610023 shu

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

School of Pharmacy, Fudan University, Shanghai 201203

Corresponding author: Liu Mingming, lmm@fudan.edu.cn Wang Yang, wangyang@shmu.edu.cn
Received Date: 13 October 2016
Revised Date: 25 November 2016

Fund Project: the National Natural Science Foundation of China 81302257the National Natural Science Foundation of China 21472025

Figures(2)

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.
- diaryl-β-lactam,
- tubulin aggregation inhibitor,
- antitumor
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