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

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 (GI values of 3.85 and 3.05 μM for VIPI and COMI human glioblastoma stem cells, respectively).

Actinobacteria Derived from Algerian Ecosystems as a Prominent Source of Antimicrobial Molecules

“…[91]. A series of polyether antibiotics including nigericin (40), epinigericin (41), abierixin (42), and the new grisorixin methyl ester (43) were isolated from the Streptomyces youssoufiensis SF10 strain collected from Chélia Mountain, in Khenchela (North-eastern Algeria) [105]. The online coupled HPLC-ESIMS analysis provided the full polyether profile, and the preparative HPLC technique in the reversed phase condition gave pure compounds, which were identified by extensive NMR and ESI-MS spectra in comparison with reported data.…”

“…Recently, the polyether antibiotics nigericin (40) and the new grisorixin methyl ester (43) isolated from Streptomyces youssoufiensis SF10 have provided significant cytotoxic activities against glioblastoma stem cells, with a higher activity for grisorixin methyl ester (GI 50 values of 3.85 and 3.05 µM for two human glioblastoma stem cell lines), corresponding to a higher growth-inhibion cell-proliferation than the drug temozolomide [105]. The data are remarkable due to both the nature of glioblastoma multiforme as the most malignant primary brain tumors and the effect against stem cells which are resistant to the conventional therapies.…”

Enhanced Production and Quantitative Evaluation of Nigericin from the Algerian Soil-Living Streptomyces youssoufiensis SF10 Strain

“…A detection limit corresponding to 1 µg/mL (1.38 µM) was also determined. Using a sample of pure nigericin previously isolated by the same SF10 strain [23], a calibration curve was constructed by plotting the ELSD response area versus nigericin concentration. The obtained calibration curve presented a very good linear fit (Figure 2).…”

“…The ionophoric polyethers nigericin, epinigericin, abierixin and the newly isolated grisorixin methyl ester were isolated in pure form from the crude ethyl acetate extract, and their structures were fully characterized by mass spectrometry and extensive NMR analysis. Furthermore, we observed that both nigericin and grisorixin methyl ester affected human glioblastoma stem cell proliferation in a dose-dependent manner, with promising GI 50 values compared with the currently used drug, temozolomide [23].…”

“…The strain was selected from the 11 Actinomycetale strains obtained, based on its ability to inhibit the growth of pathogenic and phytopathogenic bacteria (methicillin-resistant Staphylococcus aureus and Bacillus subtilis) as well as fungi (Fusarium oxysporum). Details on the strain identification were reported by Leulmi et al [23].…”