Anti-proliferative activity of Monensin and its tertiary amide derivatives

Bioorg Med Chem Lett. 2015 Oct 15;25(20):4539-43. doi: 10.1016/j.bmcl.2015.08.067. Epub 2015 Aug 28.

Abstract

New tertiary amide derivatives of polyether ionophore Monensin A (MON) were synthesised and their anti-proliferative activity against cancer cell lines was studied. Very high activity (IC50=0.09 μM) and selectivity (SI=232) of MON against human biphenotypic myelomonocytic leukemia cell line (MV4-11) was demonstrated. The MON derivatives obtained exhibit interesting anti-proliferative activity, high selectivity index and also are able to break the drug-resistance of cancer cell line.

Keywords: Anti-proliferative activity; Natural products; Polyether ionophores; Selectivity; Tertiary amides.

MeSH terms

  • Amides / chemistry*
  • Amides / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Monensin / analogs & derivatives*
  • Monensin / chemical synthesis
  • Monensin / chemistry
  • Monensin / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amides
  • Antineoplastic Agents
  • Monensin