Synthesis and in vitro investigation of halogenated 1,3‐bis(4‐nitrophenyl)triazenide salts as antitubercular compounds

Abstract

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 μm. 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 μm, 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.

Seeking potent anti-tubercular agents: design and synthesis of substituted-N-(6-(4-(pyrazine-2-carbonyl)piperazine/homopiperazine-1-yl)pyridin-3-yl)benzamide derivatives as anti-tubercular agents

“…All compounds (6a-n and 7a-m) were screened for their in vitro anti-TB activity towards Mtb H37Ra. 31 H37Ra is an attenuated tubercle bacillus strain closely related to the virulent type strain M. tuberculosis H37Rv. Several compounds signicantly inhibited the growth at micro molar to submicromolar levels.…”

In vitro and in vivo Evaluation of in silico Predicted Pneumococcal UDPG:PP Inhibitors

“…Minimal inhibitory concentrations (MIC) of all compounds were determined using a resazurin assay as described previously ( Torfs et al, 2018 ). Briefly, 100 μL of a ½ serial dilution series of compounds in BHI broth was added to 96-well plates, after which bacteria were added to a final concentration of 2.5 × 10 5 CU/mL in 200 μL.…”

Chemical Detection of Short-Lived Species Induced in Aqueous Media by Atmospheric Pressure Plasma

“…An example of a spin probe is 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH). CMH is a cyclic hydroxylamine, which reacts with superoxide radicals to form a nitroxide radical detected by EPR: =N▬OH → =N▬O• [46]. However, this method is mostly used in biological systems rather than plasma-liquid systems.…”

“…Here, peroxynitrite was only detected in highly basic solutions, confirming its short life at neutral pH. Xu et al used 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine (a hydroxylamine) to detect both superoxide radical anion and peroxynitrite anion via EPR analysis of the formed 4-oxo-2,2,6,6-tetramethylpiperidine 1-oxyl [87] (distinguishing between the two is not possible with this method [46,87]).…”