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Optimization of IG-105 (1) on the carbazole ring provided five series of new carbazole sulfonamides derivatives, 7a-e, 8a-g, 9a-g, 10a-e, and 11a-g. All of the compounds were evaluated against HepG2, MCF-7, MIA PaCa-2, and Bel-7402 cells for antiproliferative activity. Each series of compounds was 2-5 times more active against HepG2 cells (IC50: 1.00-10.0 μM) than the other three tumor cell lines. Several representative compounds, selected from each series, showed aqueous solubility (13.4-176.5 µg/mL at pH 7.4 and 2.0) better than 1, with the aqueous solubility of corresponding salts > 30 mg/mL. From the results of evaluating the effects of the compounds 7b, 8c, 9c, 10c and 11c on tubulin in vitro, we speculated that their targets were different from those of 1 and CA-4P. We tested the antitumor activity of the representative compound 7b·HCl (10 mg/kg) in an in vivo study and found that its tumor growth inhibition rate was 41.1%. The tumor growth inhibition rate of 7b·HCl (20 mg/kg) was 54.6%, whereas the tumor growth inhibition rate of CA-4P (50 mg/kg) was 48.3%. And in another batch of in vivo antitumor activity testing, 9c·HCl and 11c·HCl at doses of 10 mg/kg resulted in 61.1% and 50.0% inhibition, respectively. These promising results warrant further development of the derivatives, which may use a novel mechanism and show potential potency as antitumor drug candidates. Copyright © 2020 Elsevier Inc. All rights reserved.


Lianqi Sun, Chenxi Wang, Xinyue Hu, Yanbin Wu, Zhi Jiang, Zhuorong Li, Xiaofang Chen, Laixing Hu. Design, synthesis, and evaluations of the antiproliferative activity and aqueous solubility of novel carbazole sulfonamide derivatives as antitumor agents. Bioorganic chemistry. 2020 Jun;99:103766

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PMID: 32247110

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