Few studies have been undertaken on the relationship of the structure of flavones and neuroprotection. Previously, we described the structural determinants of the neuroprotective activity of some natural flavones in cerebellar granule neurons in culture against an oxidative insult (H2O2). In the present work, we analyzed anti-oxidant activity, cellular iron, and Ca2+ levels and cellular bioavailability of neuroprotective and nonneuroprotective flavones in the same experimental paradigm. Oxidative cellular damage produced by H2O2 was prevented by all of the studied flavones with rather similar potency for all of them. Labile Iron Pool was neither affected by protective nor nonprotective flavones. Intracellular Ca2+ homeostasis was not affected by protective flavones either. Nonetheless, fisetin, the nonprotective flavone, decreased Ca2+ levels modifying Ca2+ homeostasis. Methylation of the catechol group, although weakens anti-oxidant capacity, keeps the neuroprotective capacity with less degradation and lower toxicity, constituting promising structural alternatives as leads for the design of neuroprotective molecules.
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Because they all share the basic backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one), the molecules studied can be primarily considered as flavones and as such are taken in this work, knowing that as hydroxyl flavones they can also be considered as flavonols.
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This work was supported by Grant L/ICA/139636 from the International Cooperation and Assistance Office of the OPCW (Organization for the Prohibition of Chemical Weapons), The Hague, The Netherlands. We thank Prof. Prem Ponka for the generous gift of the iron chelator SIH.
Conflict of interest
The authors declare no conflicts of interest.
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Echeverry, C., Arredondo, F., Martínez, M. et al. Antioxidant Activity, Cellular Bioavailability, and Iron and Calcium Management of Neuroprotective and Nonneuroprotective Flavones. Neurotox Res 27, 31–42 (2015). https://doi.org/10.1007/s12640-014-9483-y