2. Academic Validation
  3. Antiproliferative activity of ester derivatives of monensin A at the C-1 and C-26 positions

Antiproliferative activity of ester derivatives of monensin A at the C-1 and C-26 positions

  • Chem Biol Drug Des. 2019 Oct;94(4):1859-1864. doi: 10.1111/cbdd.13581.
Greta Klejborowska 1,  Marta Jędrzejczyk 1,  Natalia Stępczyńska 1,  Ewa Maj 2,  Joanna Wietrzyk 2,  Adam Huczyński 1
Affiliations

Affiliations

  • 1 Department of Bioorganic Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Poznań, Poland.
  • 2 Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
PMID: 31260603 DOI: 10.1111/cbdd.13581
Abstract

Monensin A (MON) is a polyether ionophore Antibiotic, which shows a wide spectrum of biological activity, including Anticancer activity. A series of structurally diverse monensin esters including its C-1 esters (1-9), C-26-O-acetylated derivatives (10-15), and lactone (16) was synthesized and for the first time evaluated for their antiproliferative activity against four human Cancer cell lines with different drug-sensitivity level. All of the MON derivatives exhibited in vitro antiproliferative activity against Cancer cells at micromolar concentrations. The majority of the compounds was able to overcome the drug resistance of LoVo/DX and MES-SA/DX5 cell lines. The most active compounds proved to be MON C-26-O-acetylated derivatives (10-15) which exhibited very good resistance index and high selectivity index.

Keywords

antiproliferative activity; drug repurposing; natural products; polyether ionophores.

Figures
Products