HYBRIDS OF OLEANOLIC ACID WITH NORBORNENE-2,3-DICARBOXIMIDE-N- CARBOXYLIC ACIDS AS POTENTIAL ANTICANCER AGENTS

Acta Pol Pharm. 2017 May;74(3):827-835.

Abstract

The synthesis and cytotoxic activity of new oleanolic acid derivatives (8a-c and 9a-c) are presented. The obtained compounds are hybrids of oleanolic acid oximes and carboxylic acids containing short alkyl chains linked with nitrogen atom of norbomene-2,3-dicarboximide moieties via the nitrogen atom. The structures of the obtained new compounds (8a-c and 9a-c) were confinmed by spectral data. The derivatives 8a-c and 9a-c were subjected to the MTT assay in order to evaluate their cytotoxic activity towards HeLa, KB, MCF-7, HepG2 and HDF cell lines in comparison to mother compound (oleanolic acid, 1). Among the tested oximes acylated with carboxylic acids containing norbomene-imide moieties, the derivative 8b, with a propionoxyimino linker, exhibited the most advantageous level of cytotoxicity, with IC50 values from 2.75 pM (for MCF-7 cells) to 4.36 pM (for HDF cells).

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / pharmacology*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery / methods
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Norbornanes / chemical synthesis*
  • Norbornanes / pharmacology*
  • Oleanolic Acid / analogs & derivatives
  • Oleanolic Acid / chemical synthesis*
  • Oleanolic Acid / pharmacology*
  • Structure-Activity Relationship
  • Technology, Pharmaceutical / methods

Substances

  • Antineoplastic Agents
  • Carboxylic Acids
  • Norbornanes
  • Oleanolic Acid