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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41598-025-92635-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cyclic N, O-acetals and corresponding opened N, N-aminals as new scaffolds with promising anti-inflammatory and antifungal activities against Candida albicans.
Sci Rep
March 2025
UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Institut National de la Santé et de la Recherche Médicale U1285, Centre National de la Recherche Scientifique, University of Lille, 59000, Lille, France.
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.
View Article and Find Full Text PDFDouble Hydride Transfer Enabled Substitution of All Hydrogens at α,β-Positions of Cyclic Amines: Access to α,β-Unsaturated Lactams.
Org Lett
February 2025
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho Koganei, Tokyo 184-8588, Japan.
A one-shot substitution of all hydrogens at the α,β-positions of saturated cyclic amines was achieved. The key feature of this reaction is the sequential involvement of intra- and intermolecular redox processes. When ,-acetals obtained through an internal redox process were treated with a catalytic amount of Zn(OTf) and an excess amount of benzylidene barbiturates, three key transformations involving intermolecular redox process occurred successively to afford α,β-unsaturated lactams in moderate to good chemical yields.
View Article and Find Full Text PDFEco-friendly α,β-C(sp)-H difunctionalization of tertiary amines sequential [1,5]-hydride transfer and hetero-Diels-Alder cyclization.
Chem Commun (Camb)
September 2024
Institute of Advanced Studies and School of Pharmaceutical Sciences, Taizhou University, 1139 Shifu Avenue Taizhou, 318000, People's Republic of China.
An unprecedented eco-friendly multi-component domino reaction for the synthesis of novel ,-acetals is reported. The protocol involves sequential coupling, [1,5]-hydride transfer and hetero-Diels-Alder cyclization. This new strategy enables direct α,β-difunctionalization of cyclic amines utilizing enamines generated .
View Article and Find Full Text PDFEosin, blue LEDs and DIPEA are employed in a simple synthesis of (poly)cyclic ,- and ,-acetals.
Chem Commun (Camb)
May 2024
Department of Chemistry, University of Crete, Vasilika Vouton, 71003, Iraklion, Crete, Greece.
A simple procedure for the synthesis of (poly)cyclic ,- and ,-acetals from various enol ethers, -acyl enamines or Boc-protected enamines has been developed. The key step is a photocatalytic Stork-Ueno-type cylization using the very simple metal-free conditions of catalytic eosin, diisopropylamine in the green solvent ethanol with blue LED irradition.
View Article and Find Full Text PDFIridium-Catalyzed Reductive (3+2) Annulation of Lactams Enabling the Rapid Total Synthesis of (±)-Eburnamonine.
Angew Chem Int Ed Engl
February 2024
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
A reductive (3+2) annulation of lactams through iridium-catalyzed hydrosilylation and photoredox coupling with α-bromoacetic acid was developed. The iridium-catalyzed hydrosilylation of the lactam carbonyl group and subsequent elimination provide a transient cyclic enamine, which undergoes iridium-catalyzed photoredox coupling with α-bromoacetic acid in a one-pot process. The developed conditions show high functional-group tolerance and provide cyclic N,O-acetals containing a quaternary carbon center.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!