Pinheiro Luís, Cipriano Catarina, Santos Filipe, Máximo Patrícia, Fernandes Eduarda, Freitas Marisa, Branco Paula S
LAQV, REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, Campus da Caparica, 2825-149 Caparica, Portugal.
LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Molecules. 2025 Jul 3;30(13):2850. doi: 10.3390/molecules30132850.
Floridoside (2--D-glycerol--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 (-, -) and acylated floridoside derivative () 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 in the presence of pyridine. The compounds were analysed for their cytotoxicity, with and 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 prevented the oxidative burst in activated human neutrophils (IC = 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.
弗罗里多苷（2--D-甘油--D-吡喃半乳糖苷）是一种天然产物，常见于红藻中。它作为藻类的碳储备，是在应对渗透和热应激时作为一种保护反应而产生的。弗罗里多苷及其酰化衍生物都与调节氧化还原稳态和炎症反应有关。因此，我们旨在评估新合成的弗罗里多苷磷酸三酯（-，-）和酰化弗罗里多苷衍生物（）是否能调节受刺激的人类中性粒细胞中的氧化爆发。合成策略包括用甘油衍生物对硫代糖苷供体进行糖基化，以NIS/TfOH作为促进剂。在吡啶存在下用POCl₃实现磷酸化。分析了这些化合物的细胞毒性，其中和在50 μM时具有细胞毒性，而其他化合物在测试浓度下未显示细胞毒性。使用多种探针[鲁米诺、氨基苯基荧光素（APF）和Amplex Red（AR）]检测中性粒细胞的氧化爆发，以评估活性物质水平。化合物阻止了活化的人类中性粒细胞中的氧化爆发（IC₅₀ = 83 ± 7 μM）。在当前实验条件下，所有其他测试化合物在抑制APF和AR氧化方面均无效。这些发现突出了基于弗罗里多苷的衍生物作为靶向炎症途径候选物的潜力。
