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Synthesis and Antibacterial Evaluation of Bis‐thiazolium, Bis‐imidazolium, and Bis‐triazolium Derivatives
Author(s) -
Thomas Benoît,
Duval Raphaël E.,
Fontanay Stéphane,
Varbanov Mihayl,
Boisbrun Michel
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900151
Subject(s) - antibacterial activity , cationic polymerization , ammonium , chemistry , minimum inhibitory concentration , toxicity , combinatorial chemistry , stereochemistry , bacteria , medicinal chemistry , in vitro , organic chemistry , biochemistry , biology , genetics
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 −1 . Some of them also exhibited low toxicity toward eukaryotic MRC‐5 lung fibroblasts, and we showed that this toxicity is clearly correlated with clog P . Finally, four selected compounds were found to exhibit a clear bactericidal effect.