Synthesis, Characterization and Anti-hepatoma Activity of New Hederagenin Derivatives

Mini Rev Med Chem. 2020;20(3):252-257. doi: 10.2174/1389557519666191010091612.

Abstract

Background: Based on the biological significance of hederagenin-type saponins found in our previous investigation, a series of new hederagenin derivatives were designed and synthesized.

Methods: Their in vitro antiproliferative activities were evaluated against the HepG2 liver cancer cell line and normal cell line L929 by MTT assay.

Results: The preliminary bioassay results demonstrated that all the tested compounds 1-7 showed potent anti-hepatoma activities, and some compounds exhibited better effects than 5-fluorouracil against human hepatocellular carcinoma HepG2 cell line. Furthermore, compound 5 showed a significant antihepatoma activity against HepG2 cells with an IC50 value of 1.88 µM. Besides, all of the tested compounds showed a low cytotoxic effect against the normal cell line L929.

Conclusion: All the compounds 1-7 displayed superior selectivity against human hepatocellular carcinoma HepG2 cell line, and the results suggest that the structural modifications of C ring on the hederagenin backbone are vital for modulating anti-hepatoma activities.

Keywords: Nigella glandulifera; anti-hepatoma; cytotoxicity; hederagenin; hederagenin-type saponin; structural modification..

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Hep G2 Cells
  • Humans
  • Liver / drug effects*
  • Liver / pathology
  • Liver Neoplasms / pathology*
  • Molecular Structure
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemical synthesis
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Oleanolic Acid
  • hederagenin