Streptogramin A derivatives as mitochondrial translation inhibitors to suppress glioblastoma stem cell growth

Sighel, Denise; Battistini, Giulia; Rosatti, Emanuele Filiberto; Vigna, Jacopo; Pavan, Matteo; Belli, Romina; Peroni, Daniele; Alessandrini, Federica; Longhi, Sara; Pancher, Michael; Rorbach, Joanna; Moro, Stefano; Quattrone, Alessandro; Mancini, Ines

doi:10.1016/j.ejmech.2022.114979

Cited by 2 publications

(1 citation statement)

References 33 publications

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“…In detail, we assessed the cytotoxic effect of 7 on GSC COMI gliomaspheres. Indeed, COMI cells show high sensitivity to alkyl polyarsenicals and have been extensively used in our previous works [ 20 , 22 ]. To this aim, 1000 COMI cells were seeded in a low attachment round-bottom plate and allowed to form a gliomasphere for 3–4 days, then the gliomaspheres were treated with different concentrations of 7 .…”

Section: Resultsmentioning

confidence: 99%

Expanding the Chemical Space of Arsenicin A-C Related Polyarsenicals and Evaluation of Some Analogs as Inhibitors of Glioblastoma Stem Cell Growth

et al. 2023

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The marine polyarsenical metabolite arsenicin A is the landmark of a series of natural and synthetic molecules characterized by an adamantane-like tetraarsenic cage. Arsenicin A and related polyarsenicals have been evaluated for their antitumor effects in vitro and have been proven more potent than the FDA-approved arsenic trioxide. In this context, we have expanded the chemical space of polyarsenicals related to arsenicin A by synthesizing dialkyl and dimethyl thio-analogs, the latter characterized with the support of simulated NMR spectra. In addition, the new natural arsenicin D, the scarcity of which in the Echinochalina bargibanti extract had previously limited its full structural characterization, has been identified by synthesis. The dialkyl analogs, which present the adamantane-like arsenicin A cage substituted with either two methyl, ethyl, or propyl chains, were efficiently and selectively produced and evaluated for their activity on glioblastoma stem cells (GSCs), a promising therapeutic target in glioblastoma treatment. These compounds inhibited the growth of nine GSC lines more potently than arsenic trioxide, with GI50 values in the submicromolar range, both under normoxic and hypoxic conditions, and presented high selectivity toward non-tumor cell lines. The diethyl and dipropyl analogs, which present favorable physical-chemical and ADME parameters, had the most promising results.

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Section: Resultsmentioning

confidence: 99%