Identification of N-Oxide-Containing Aromatic Heterocycles as Pharmacophores for Rumen Fermentation Modifiers

Different strategies have been used to mitigate greenhouse gas emissions from domesticated ruminants, including the removal of protozoa (defaunation). The objective of the present work was to analyze the potential of different N-oxide-containing aromatic heterocycles with known antiprotozoal activity as rumen-gas-abating agents. Nineteen pure compounds, belonging to seven different N-oxide chemotypes from our chemo-library were studied together with monensin in an in vitro rumen simulation assay. Fermentation profiles, i.e., gas production, pH, and short carboxylic acid concentrations, were compared to an untreated control at 96 h post inoculation. In our study, we investigated whole-ruminal fluid, with and without compound treatments, by NMR spectroscopy focusing on concentrations of the metabolites acetate, propionate, butyrate, and lactate. From data analysis, three of the compounds from different N-oxide chemotypes, including quinoxaline dioxide, benzofuroxan, and methylfuroxan, were able to diminish the production of gases such as monensin with similar gas production lag times for each of them. Additionally, unlike monensin, one methylfuroxan did not decrease the rumen pH during the analyzed incubation time, shifting rumen fermentation to increase the molar concentrations of propionate and butyrate. These facts suggest interesting alternatives as feed supplements to control gas emissions from dairy ruminants.