Floridoside Phosphotriester Derivatives: Synthesis and Inhibition of Human Neutrophils’ Oxidative Burst

Floridoside (2-<i>O</i>-D-glycerol-<i>α</i>-D-galactopyranoside) is a natural product typically found in red algae. It serves as the algae’s carbon reserve and is produced as a protective response against osmotic and heat stress. Both floridoside and its acylated derivatives...

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Main Authors: Luís Pinheiro, Catarina Cipriano, Filipe Santos, Patrícia Máximo, Eduarda Fernandes, Marisa Freitas, Paula S. Branco
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/13/2850
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Summary:Floridoside (2-<i>O</i>-D-glycerol-<i>α</i>-D-galactopyranoside) is a natural product typically found in red algae. It serves as the algae’s carbon reserve and is produced as a protective response against osmotic and heat stress. Both floridoside and its acylated derivatives have been associated with modulating redox homeostasis and inflammatory responses. Therefore, we aimed to evaluate whether the newly synthesized floridoside phosphotriesters (<b>1b</b>–<b>1d</b>, <b>1f</b>–<b>1h</b>) and acylated floridoside derivative (<b>1e</b>) can modulate the oxidative burst in stimulated human neutrophils. Synthetic strategies included the glycosylation of the thioglycoside donor with glycerol derivatives, having NIS/TfOH as the promoter. Phosphorylation was achieved with POCl<sub>3</sub> in the presence of pyridine. The compounds were analysed for their cytotoxicity, with <b>1b</b> and <b>1h</b> being cytotoxic at 50 μM, while the others showed no cytotoxicity in the tested concentrations. The detection of the neutrophils’ oxidative burst was performed using multiple probes [luminol, aminophenyl fluorescein (APF), and Amplex Red (AR)] to evaluate reactive species levels. Compound <b>1e</b> prevented the oxidative burst in activated human neutrophils (IC<sub>50</sub> = 83 ± 7 μM). All the other tested compounds were ineffective in inhibiting APF and AR oxidation under the present experimental conditions. These findings highlight the potential of floridoside-based derivatives as candidates for targeting inflammatory pathways.
ISSN:1420-3049