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
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Date
2018-03-07
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taylor francis
Abstract
ABSTRACT
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 chromatographyelectrospray
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).