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

## TL;DR

Scientists synthesized new versions of a compound found in red algae and found one of them can reduce inflammation in human neutrophils.

## Contribution

The study reports the synthesis and evaluation of new floridoside derivatives for their ability to inhibit oxidative burst in neutrophils.

## Key findings

- Compound 1e inhibited the oxidative burst in activated human neutrophils with an IC50 of 83 ± 7 μM.
- Compounds 1b and 1h were cytotoxic at 50 μM, while others were not cytotoxic at tested concentrations.
- Only compound 1e showed inhibitory activity, while others were ineffective in reducing reactive species levels.

## Abstract

Floridoside (2-O-D-glycerol-α-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 (1b–1d, 1f–1h) and acylated floridoside derivative (1e) 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 POCl3 in the presence of pyridine. The compounds were analysed for their cytotoxicity, with 1b and 1h 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 1e prevented the oxidative burst in activated human neutrophils (IC50 = 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.