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 1 H 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 antiproliferative activities. Among them, (S)-1-(3,4,5-trimethoxyphenyl)-4-(3-(4-nitrobenzoyloxyl)-4-methoxyphenyl)-3-methylene-azetidin-2-one (5n) exhibited most potent activities against the above four cancer cells with the corresponding IC 50 values of 0.055, 0.105, 0.084 and 0.102 μmol/L, respectively, indicating that these type of compounds merit further investigation.
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