Fiche publication
Date publication
mai 2019
Journal
ChemMedChem
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOISBRUN Michel
Tous les auteurs :
Thomas B, Duval RE, Fontanay S, Varbanov M, Boisbrun M
Lien Pubmed
Résumé
Given the worldwide spread of bacterial drug resistance, there is an urgent need to develop new compounds that exhibit potent antibacterial activity and that are unimpaired by this phenomenon. Quaternary ammonium compounds have been used for many years as disinfectants, but recent advances have shown that polycationic derivatives exhibit much stronger activity and are less prone to bacterial resistance than commonly used monocationic compounds. In this sense, we prepared three series of new bis-cationic compounds: bis-thiazoliums, bis-imidazoliums, and bis-1,2,4-triazoliums. If some compounds of the first series showed fair antibacterial activity, most of those belonging to the two other series were highly potent, with minimum inhibitory concentrations close to 1 μg mL . Some of them also exhibited low toxicity toward eukaryotic MRC-5 lung fibroblasts, and we showed that this toxicity is clearly correlated with clogP. Finally, four selected compounds were found to exhibit a clear bactericidal effect.
Mots clés
1,2,4-triazolium, antibacterial agents, clogP, cytotoxicity, imidazolium
Référence
ChemMedChem. 2019 May 22;:
