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

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 Et acetate ext. was analyzed by high performance liq. chromatog.-​electrospray ionization mass spectrometry, leading to the detection of the ionophoric polyethers nigericin, epinigericin, abierixin and the newly isolated grisorixin Me ester. The presence of epimeric forms of nigericin​/epinigericin and grisorixin​/epigrisorixin has spurred d. functional theory computational calcns. This anal. 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 Me ester showed to affect glioblastoma stem cells proliferation in a dose-​dependent manner, with a higher activity for the more lipophilic grisorixin Me ester (GI50 values of 3.85 and 3.05 μM for VIPI and COMI human glioblastoma stem cells, resp.)​.