Wydział Chemii

Mariusz Dziadas

Elżbieta Gębarowska

Ksenia Wójtowicz

Alicia Domínguez-Martín

2026

Carbohydrate Research

565

109935/1-109935/9

10.1016/j.carres.2026.109935

Naukowa

Angielski

Artykuł

Thiamphenicol (TAM) is an amphenicol antibiotic widely used in veterinary medicine, whose efficacy is increasingly compromised by enzymatic inactivation mediated by chloramphenicol acetyltransferases (CATs). These enzymes acetylate the 3-hydroxyl group of phenicols, abolishing ribosomal binding and antibacterial activity. Here, we report the synthesis and evaluation of thiamphenicol-3-O-β-d-glucopyranoside (TAMG) as a glucosidic prodrug designed to mask the CAT-susceptible site. TAMG was obtained via Schmidt glucosylation followed by Zemplén deprotection and fully characterized by NMR and HPLC-MS. In contrast to TAM, TAMG showed complete resistance to CAT-mediated acetylation in vitro, consistent with steric shielding of the 3-OH group. Electrochemical stress testing revealed enhanced redox robustness of the glucosylated derivative. In vivo evaluation using a Galleria mellonella infection model demonstrated that TAMG was non-toxic up to 100 mg/kg and provided complete protection against Salmonella enterica infection across the tested dose range in the Galleria mellonella model, without the need for exogenous β-glucosidase activation. These findings highlight 3-O-glucosylation as a practical strategy to overcome CAT-driven resistance in veterinary phenicol therapy.

Thiamphenicol, 3-O-β-d-glucopyranoside, Glucosylation, Prodrug, Chloramphenicol acetyltransferase, Electrochemistry-MS, Galleria mellonella, Veterinary antibiotic, Salmonella enterica

http://dx.doi.org/10.1016/j.carres.2026.109935

http://www.elsevier.com