Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives.

Yingqian Liu, Keduo Qian, Chih-Ya Wang, Chin-Ho Chen, Xiaoming Yang, Kuo-Hsiung Lee

Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA.

Bioorganic & medicinal chemistry letters 2012 Dec 15

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Eighteen novel spin-labeled 18β-glycyrrhetinic acid (GA) derivatives were designed, synthesized, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU-145, KB and KBvin). Most of the derivatives showed more significant cytotoxicity than that of the parent compound GA. The best compound, 6j, with a tryptophan amino moiety and piperidine nitroxyl radical showed GI(50) values of 13.7-15.0 μM, and was fivefold more potent than GA. In a mechanism of action study, compound 7a was confirmed as a 20S proteasome inhibitor in both in vitro and cell-based assays. These findings support further optimization efforts based on 18β-GA as a lead compound to develop potential anticancer drug candidates. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Yingqian Liu, Keduo Qian, Chih-Ya Wang, Chin-Ho Chen, Xiaoming Yang, Kuo-Hsiung Lee. Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives. Bioorganic & medicinal chemistry letters. 2012 Dec 15;22(24):7530-3