Nigericin and grisorixin methyl ester from the Algerian soil-living Streptomyces youssoufiensis SF10 strain: a computational study on their epimeric structures and evaluation of glioblastoma stem cells growth inhibition

Nat Prod Res. 2019 Jan;33(2):266-273. doi: 10.1080/14786419.2018.1446014. Epub 2018 Mar 7.


The present work describes the metabolites produced by a strain identified as Streptomyces youssoufiensis, whose secondary metabolites profile has not been studied so far. The crude ethyl acetate extract was analyzed by high performance liquid chromatography-electrospray ionization mass spectrometry, leading to the detection of the ionophoric polyethers nigericin, epinigericin, abierixin and the newly isolated grisorixin methyl ester. The presence of epimeric forms of nigericin/epinigericin and grisorixin/epigrisorixin has spurred density functional theory computational calculations. This analysis was able to provide the relative stability of the most favored epimers, setting the basis for general structural considerations applicable to several other polyethers. Both nigericin sodium salt and grisorixin methyl ester showed to affect glioblastoma stem cells proliferation in a dose-dependent manner, with a higher activity for the more lipophilic grisorixin methyl ester (GI50 values of 3.85 and 3.05 μM for VIPI and COMI human glioblastoma stem cells, respectively).

Keywords: DFT calculation; HPLC-ESI/MS; Streptomyces; cytotoxicity; glioblastoma; polyethers.

MeSH terms

  • Anti-Bacterial Agents / isolation & purification
  • Cell Proliferation / drug effects
  • Chromatography, High Pressure Liquid
  • Density Functional Theory
  • Glioblastoma / pathology
  • Humans
  • Molecular Structure
  • Nigericin / analogs & derivatives*
  • Nigericin / isolation & purification*
  • Nigericin / metabolism*
  • Spectrometry, Mass, Electrospray Ionization
  • Stem Cells / pathology
  • Stereoisomerism
  • Streptomyces / chemistry*
  • Tumor Cells, Cultured


  • Anti-Bacterial Agents
  • grisorixin
  • Nigericin