Article Dans Une Revue Scientific Reports Année : 2025

Cyclic N, O-acetals and corresponding opened N, N-aminals as new scaffolds with promising anti-inflammatory and antifungal activities against Candida albicans

Résumé

P2 × 7R is crucial in the pathogenesis of chronic inflammatory diseases, and its activation leads to the release of pro-inflammatory cytokines, exacerbating the inflammatory response. Two new series of scarce cyclic N, O-acetals (ATF 61-74) and corresponding opened N, N-aminals (CS 1-14) have been designed as novel potential P2RX7 antagonists, then synthesized and evaluated for their anti-inflammatory properties through investigating the pro-inflammatory markers and also for their antifungal activity against Candida albicans. Three compounds (ATF 64, CS 8, and CS 9) exhibited dual antifungal and anti-inflammatory properties. ATF 64, CS 8, and CS 9 reduced ROS production and IL-1β expression in macrophages and intestinal cells in a manner correlated with NF-KB expression. These compounds showed excellent antifungal activity against clinical isolates of C. albicans resistant to fluconazole and caspofungin, and reduced C. albicans biofilm formation. Treatment with CS 8 or CS 9 protected the nematode Caenorhabditis elegans against infection with C. albicans and enhanced antimicrobial gene expression. This duality of action offers a promising new pharmacological strategy to counteract inflammatory diseases and propels N, N-aminals as promising candidates for future optimization and investigation.

Domaines

Fichier principal
Vignette du fichier
41598_2025_Article_92635.pdf (3.51 Mo) Télécharger le fichier
Origine Publication financée par une institution
Licence

Dates et versions

hal-05025621 , version 1 (02-04-2026)

Licence

Identifiants

Citer

Christine Safi, Louis Camaioni, Mohamed Othman, Dylan Lambert, Mathys Buisine, et al.. Cyclic N, O-acetals and corresponding opened N, N-aminals as new scaffolds with promising anti-inflammatory and antifungal activities against Candida albicans. Scientific Reports, 2025, 15 (1), pp.8364. ⟨10.1038/s41598-025-92635-z⟩. ⟨hal-05025621⟩
129 Consultations
35 Téléchargements

Altmetric

Partager

  • More