Introduction: Neurodegenerative disorders (NDs) are characterized by progressive neuronal loss. Since multitarget therapy represents a promising approach, we investigated congeners of resveratrol (RSV).1 Some new stilbenols achieved antioxidant activity, together with strong inhibition of MAO and carbonic anidrases.2 The aim of this project is to further explore their pharmacological potential against key pathological features associated with Alzheimer’s disease (AD). Material & Methods: The multitarget activity was evaluated using in vitro assays on ChEs, supported by molecular docking studies. Antioxidant activity was measured with the ABTS assay. C. elegans served as an in vivo AD model. Anti-aggregation effects on β-amyloid (Aβ) peptides were evaluated via the thioflavin-T (ThT) assay. Basal ATP levels in SH-SY5Y neuroblastoma cells were measured via bioluminescence assay. Physicochemical properties were also studied. Results: The stilbenols showed promising multitarget activity, mitigating major AD hallmarks in vitro and in silico, antioxidant and anti-cholinesterase activity in the low micromolar range. They inhibited extracellular Aβ aggregation and enhanced resistance to oxidative stress. ATP levels showed a tendency to increase after incubation, indicating a positive effect on cellular energy supply. They exhibited high passive permeability and favorable ADME properties. Conclusion: The stilbenol derivatives investigated demonstrate potential as multitarget agents useful for NDs.
SYNTHETIC RESVERATROL ANALOGUES ENDOWED WITH POTENTIAL NEUROPROTECTIVE AND ANTIOXIDANT ACTIVITIES: BIOCHEMICAL AND BIOPHYSICAL PROFILING
Barbara De Filippis;Marialuigia Fantacuzzi;Alessandra Ammazzalorso;
2026-01-01
Abstract
Introduction: Neurodegenerative disorders (NDs) are characterized by progressive neuronal loss. Since multitarget therapy represents a promising approach, we investigated congeners of resveratrol (RSV).1 Some new stilbenols achieved antioxidant activity, together with strong inhibition of MAO and carbonic anidrases.2 The aim of this project is to further explore their pharmacological potential against key pathological features associated with Alzheimer’s disease (AD). Material & Methods: The multitarget activity was evaluated using in vitro assays on ChEs, supported by molecular docking studies. Antioxidant activity was measured with the ABTS assay. C. elegans served as an in vivo AD model. Anti-aggregation effects on β-amyloid (Aβ) peptides were evaluated via the thioflavin-T (ThT) assay. Basal ATP levels in SH-SY5Y neuroblastoma cells were measured via bioluminescence assay. Physicochemical properties were also studied. Results: The stilbenols showed promising multitarget activity, mitigating major AD hallmarks in vitro and in silico, antioxidant and anti-cholinesterase activity in the low micromolar range. They inhibited extracellular Aβ aggregation and enhanced resistance to oxidative stress. ATP levels showed a tendency to increase after incubation, indicating a positive effect on cellular energy supply. They exhibited high passive permeability and favorable ADME properties. Conclusion: The stilbenol derivatives investigated demonstrate potential as multitarget agents useful for NDs.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
