Design and Synthesis of New Anticancer Glycyrrhetinic Acids and Oleanolic Acids

Biol Pharm Bull. 2017;40(5):703-710. doi: 10.1248/bpb.b17-00016.

Abstract

A series of new glycyrrhetinic acids and oleanolic acids has been designed and synthesized based on the principles of combinatorial chemical synthesis. Their anticancer activities were further studied by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method with hepatocellular carcinoma (Hep-G2), breast cancer (MCF-7) cell lines and a normal hepatic cell (LO2). Cytotoxicity tests (in vitro) indicated that compound 6a showed the highest cytotoxicity with the lowest IC50 values of 23.34 µM on Hep-G2 cells, 12.23 µM on MCF-7 cells, and 44.47 µM on LO2, which would widen the structural diversity of these anticancer targets and confirm the perspectives of further investigations.

Keywords: anticancer; glycyrrhetinic acid; oleanolic acid; synthesis.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Glycyrrhetinic Acid / analogs & derivatives*
  • Glycyrrhetinic Acid / chemical synthesis*
  • Glycyrrhetinic Acid / chemistry
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemical synthesis*
  • Oleanolic Acid / chemistry
  • Structure-Activity Relationship
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Antineoplastic Agents
  • Tetrazolium Salts
  • Thiazoles
  • Oleanolic Acid
  • thiazolyl blue
  • Glycyrrhetinic Acid