Hederagenin as a triterpene template for the development of new antitumor compounds

Eur J Med Chem. 2015 Nov 13:105:57-62. doi: 10.1016/j.ejmech.2015.10.006. Epub 2015 Oct 9.

Abstract

In this study, a series of novel C-28 esters and amides derivatives of hederagenin (He) were designed and synthesized in attempt to develop potent antitumor agents. Their structures were confirmed by MS, IR, (1)H NMR and (13)C NMR spectroscopic analyses and their cytotoxic activities were screened in SRB assays using a panel of six human cancer cell lines. Although most of the compounds displayed moderate to high levels of cytotoxic activity they were all more potent than the natural product He. The most active compounds had either an ethylpyrimidinyl (27) or an ethylpyrrolidinyl (28) substituent, with EC50 in the range of 1.1-6.5 μM for six human cancer cell lines. Notably, this corresponds to an approximately 30-fold times greater potency than He.

Keywords: Folk medicinal plant; Hederagenin derivatives; Pentacyclic triterpenes; SRB assay; Sapindus saponaria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • 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