The tetracycline antibiotics have experienced multiple challenges in application over the years. Investigation of these compounds and their interactions with divalent metals have provided valuable insights into alterative functions for some of the established tetracycline compounds. These are studied in oxygenated systems (e.g. peroxides, catechols) in which the available binding sites can influence the oxidative activity of metallo-antibiotics. This project elucidated the binding activity of tetracycline (TTC) and oxy-tetracycline (oxy-TTC) with divalent transition metal (Cu3+) commonly found in biological systems. The catalytic activities of these the cupric complexes toward the oxidation of 3,5-di-t-butylcatechol have been investigated with kinetics, showing enzyme-like pre-equilibrium kinetics with Cu-TTC (Km = 0.44 mM ± 0.12, kcat = 3.62×10-5 s-1, kcat/Km = 8.23×10-5 mM-1s-1), Cu-oxyTTC (Km = 7.65 mM, kcat = 6.10×10-6 s-1, kcat/Km = 7.98×10-7 mM-1s-1). The reactivity of Cu-TTC was also investigated for hydrogen peroxide, under steady state kinetics (Cu-TTC: Km = 0.118 mM ± 0.0720, kcat = 3.76×10-3 s-1, kcat/Km=3.19×10-4 mM-1s-1). Near-physiological acidity conditions (pH ≈ 7.4) were simulated to observe the effects of Cu-TTC under these circumstances and its catalytic potential in presence of bicarbonate. These results may provide further insights into the role played by metallo-tetracyclines in Oxidative stress mechanisms.

Metallo-antibiotics as participant in oxidative stress mechanisms

2019 Spring National Meeting

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