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    A range of novel 1,9-disubstituted β-carboline derivatives was designed, synthesized and evaluated as potential anticancer agents. The preliminary study suggested that compounds 6a, 6b, 6c, 6d, 6e, 6f, 6g, and 6h tested in this study exerted potent antiproliferative effects on ten selected human tumor cell lines, with compound 6e being the most effective antiproliferative agent against the BGC-823, A375 and HT-29 cell lines, with IC50 values of 23.9, 9.3, and 3.6 µM, respectively. In addition, the antitumor capability of compound 6e was also evaluated in vivo, which demonstrated that compound 6e distinctly inhibited colorectal tumor growth in syngeneic BALB/c mice. Further research into the fundamental mechanism revealed that compound 6e inhibited colorectal cancer growth through the ATG5 (autophagy-related-5)/ATG7 (autophagy-related-7)-dependent autophagy pathway. This research can contribute to further clinical application of β-carboline derivatives as new antitumor drugs. Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.


    Fangrui Zhao, Jingsheng Ao, Feng Zeng, Rihui Cao, Xiangpan Li. Design, synthesis and mechanism of action of novel 1,9-disubstituted β-carboline derivatives as antitumor agents. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022 Sep;153:113494

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    PMID: 36076587

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