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 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).
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Acknowledgements
N. L. is grateful for grants provided by the scholarship program sustained by the Algerian Ministry of Higher Education. The authors thank Adriano Sterni, Mario Rossi Nicola Bazzanella at University of Trento for their technical support. Many thanks to Antonio Daga, San Martino Hospital in Genova (Italy) for cell lines gift, to Alessandro Quattrone, Director of CIBIO, for the access to the facilities and to Alessia Soldano for reading the manuscript.