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

Publication ,  Journal Article
Liu, Y; Qian, K; Wang, C-Y; Chen, C-H; Yang, X; Lee, K-H
Published in: Bioorg Med Chem Lett
December 15, 2012

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.

Duke Scholars

Published In

Bioorg Med Chem Lett

DOI

EISSN

1464-3405

Publication Date

December 15, 2012

Volume

22

Issue

24

Start / End Page

7530 / 7533

Location

England

Related Subject Headings

  • Structure-Activity Relationship
  • Proteasome Inhibitors
  • Proteasome Endopeptidase Complex
  • Molecular Conformation
  • Medicinal & Biomolecular Chemistry
  • Humans
  • Glycyrrhetinic Acid
  • Drug Screening Assays, Antitumor
  • Dose-Response Relationship, Drug
  • Cell Proliferation
 

Citation

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Liu, Y., Qian, K., Wang, C.-Y., Chen, C.-H., Yang, X., & Lee, K.-H. (2012). Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives. Bioorg Med Chem Lett, 22(24), 7530–7533. https://doi.org/10.1016/j.bmcl.2012.10.041
Liu, Yingqian, Keduo Qian, Chih-Ya Wang, Chin-Ho Chen, Xiaoming Yang, and Kuo-Hsiung Lee. “Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives.Bioorg Med Chem Lett 22, no. 24 (December 15, 2012): 7530–33. https://doi.org/10.1016/j.bmcl.2012.10.041.
Liu Y, Qian K, Wang C-Y, Chen C-H, Yang X, Lee K-H. Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives. Bioorg Med Chem Lett. 2012 Dec 15;22(24):7530–3.
Liu, Yingqian, et al. “Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives.Bioorg Med Chem Lett, vol. 22, no. 24, Dec. 2012, pp. 7530–33. Pubmed, doi:10.1016/j.bmcl.2012.10.041.
Liu Y, Qian K, Wang C-Y, Chen C-H, Yang X, Lee K-H. Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives. Bioorg Med Chem Lett. 2012 Dec 15;22(24):7530–7533.
Journal cover image

Published In

Bioorg Med Chem Lett

DOI

EISSN

1464-3405

Publication Date

December 15, 2012

Volume

22

Issue

24

Start / End Page

7530 / 7533

Location

England

Related Subject Headings

  • Structure-Activity Relationship
  • Proteasome Inhibitors
  • Proteasome Endopeptidase Complex
  • Molecular Conformation
  • Medicinal & Biomolecular Chemistry
  • Humans
  • Glycyrrhetinic Acid
  • Drug Screening Assays, Antitumor
  • Dose-Response Relationship, Drug
  • Cell Proliferation