One-pot synthesis and antiproliferative activity of novel double-modified derivatives of the polyether ionophore monensin A

Chem Biol Drug Des. 2018 Aug;92(2):1537-1546. doi: 10.1111/cbdd.13320. Epub 2018 May 18.

Abstract

Monensin A (MON) is a polyether ionophore antibiotic, which shows a wide spectrum of biological activity. New MON derivatives such as double-modified ester-carbonates and double-modified amide-carbonates were obtained by a new and efficient one-pot synthesis with triphosgene as the activating reagent and the respective alcohol or amine. All new derivatives were tested for their antiproliferative activity against two drug-sensitive (MES-SA, LoVo) and two drug-resistant (MES-SA/DX5, LoVo/DX) cancer cell lines, and were also studied for their antimicrobial activity against different Staphylococcus aureus and Staphylococcus epidermidis bacterial strains. For the first time, the activity of MON and its derivatives against MES-SA and MES-SA/DX5 were evaluated.

Keywords: antimicrobial activity; antiproliferative activity; drug design; natural compounds; polyether ionophores.

MeSH terms

  • Amides / chemistry
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Humans
  • Ionophores / chemistry*
  • Microbial Sensitivity Tests
  • Monensin / chemistry*
  • Monensin / pharmacology
  • Staphylococcus aureus / drug effects
  • Staphylococcus epidermidis / drug effects
  • Structure-Activity Relationship

Substances

  • Amides
  • Anti-Bacterial Agents
  • Ionophores
  • Monensin