Reaction of tetracycline with biologically relevant chloramines

Helicobacter pylori (H. pylori) infection triggers inflammatory processes with the consequent production of hypochlorous acid (HOG), monochloramine (NH2CI), and protein-derived chloramines. As the therapy for eradicating H. pylori is partially based on the use of tetracycline, we studied the kinetic of its consumption elicited by HOCI, NH2CI, N-chloro-n-butylamine (NHCI-But, used as a lysine-derived chloramine model), and lysozyme-derived chloramines. In the micromolar concentration range, tetracycline reacted rapidly with HOG, generating in the first few seconds intermediates of short half-life. In contrast, a slow tetracycline consumption was observed in the presene of high NH2CI and NHCI-But concentrations (millimolar range). Similar chlorinated.products of tetracycline were identified by mass spectrometry, in the presence of HOCI and NH2CI. These results evidenced that tautomers of tetracycline are pivotal intermediates in all reactions. In spite of the low reactivity of chloramines towards tetracycline, it is evident that, in the concentration range where they are produced in a H. pylori infection (millimolar range), the reactions lead to oxidation and/or chlorination of tetracycline. This kind of reactions, which were also observed triggered by lysozyme-derived chloramines, could limit the efficiency of the tetracycline -based therapy. (C) 2017 Elsevier B.V. All rights reserved.