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Synthesis and in vitro investigation of halogenated 1,3‐bis(4‐nitrophenyl)triazenide salts as antitubercular compounds
Author(s) -
Torfs Eveline,
Vajs Jure,
Macedo Maíra Bidart,
Cools Freya,
Vanhoutte Bieke,
Gorbanev Yury,
Bogaerts Annemie,
Verschaeve Luc,
Caljon Guy,
Maes Louis,
Delputte Peter,
Cos Paul,
Košmrlj Janez,
Cappoen Davie
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13087
Subject(s) - substituent , chemistry , in vitro , potency , mycobacterium tuberculosis , cationic polymerization , aryl , stereochemistry , trifluoromethyl , combinatorial chemistry , organic chemistry , biochemistry , tuberculosis , medicine , alkyl , pathology
The diverse pharmacological properties of the diaryltriazenes have sparked the interest to investigate their potential to be repurposed as antitubercular drug candidates. In an attempt to improve the antitubercular activity of a previously constructed diaryltriazene library, eight new halogenated nitroaromatic triazenides were synthesized and underwent biological evaluation. The potency of the series was confirmed against the Mycobacterium tuberculosis lab strain H37Ra, and for the most potent derivative, we observed a minimal inhibitory concentration of 0.85 μ m . The potency of the triazenide derivatives against M. tuberculosis H37Ra was found to be highly dependent on the nature of the halogenated phenyl substituent and less dependent on cationic species used for the preparation of the salts. Although the inhibitory concentration against J774A.1 macrophages was observed at 3.08 μ m , the cellular toxicity was not mediated by the generation of nitroxide intermediate as confirmed by electron paramagnetic resonance spectroscopy, whereas no in vitro mutagenicity could be observed for the new halogenated nitroaromatic triazenides when a trifluoromethyl substituent was present on both the aryl moieties.