Concise synthesis and antibacterial evaluation of novel 3‐(1, 4‐disubstituted‐1, 2, 3‐triazolyl)uridine nucleosides. Issue 11 (1st October 2018)

• Record Type: Journal Article
• Authors: Tachallait, Hamza; Bouyahya, Abdelhakim; Talha, Aicha; Bakri, Youssef; Dakka, Nadia; Demange, Luc; Benhida, Rachid; Bougrin, Khalid
• Is Part Of: Archiv der Pharmazie. Volume 351:Issue 11(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-10-01
• Subjects: antibacterial activity -- bactericidal action -- click chemistry -- microwaves -- ultrasounds -- uridine analogues, 1, 2, 3‐triazoles; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201800204
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: We report herein a simple and efficient synthesis of a new series of antibacterial uridine nucleosides. The strategy involved a sequential silylation/ N ‐glycosylation/ N ‐propargylation procedure of uracil1 for preparing the dipolarophile5 in good yield. A series of novel uridine‐[1, 2, 3]triazole nucleosides6a –j were efficiently synthesized via the copper‐catalyzed azide–alkyne cycloaddition (CuAAC) from dipolarophile5 with different selected azides. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvements were observed when reactions were carried out under sonication. Their antibacterial potential has been evaluated by means of a micro‐dilution assay against either Gram‐positive or Gram‐negative bacteria. Compounds6i and6j have shown significant bactericidal activity against Staphylococcus aureu s (MIC = 10 and 6 μM, respectively), and6h against Escherichia coli (MIC = 8 μM). Moreover, antibacterial kinetic assays showed that6i and6j significantly reduced the S. aureus growth rate at the MIC concentration, after 6 h, compared to their deprotected analogs, 6k and6l, respectively. Compound6h also significantly reduced the growth of E. coli . These antibacterial effects may be related to the penetrating properties of these compounds, as revealed by the leakage of nucleic acids from the sensitive strains. Abstract : Novel uridine‐[1, 2, 3]triazole nucleosides6a–j were synthesized and tested for their antibacterial potential against Gram‐positive and ‐negative bacteria. Compounds6i and6j show significant bactericidal activity against Staphylococcus aureu s (MIC = 10 and 6 µM, respectively), and6h against Escherichia coli (MIC = 8 µM), which may be related to the penetrating properties of these compounds revealed by leakage of nucleic acids from the sensitive strains.