Influence of oxo-derivatives of nitrogen containing heterocycles CBR-384 and CBR-386 on respiratory activity and the level of extracellular sulfur containing compounds in Escherichia coli

The biological activity of two representatives of oxo-derivative nitrogen-containing heterocycles CBR-384 and CBR-386, planned for use as drugs, on growing aerobically gram-negative bacteria Escherichia coli was studied. Compound CBR-384 completely inhibited growth rate and biomass accumulation as measured by optical density (OD600). Continuous recording of dissolved oxygen (dO2) with a Clark electrode directly in the growing culture showed that CBR-384 caused a rapid and irreversible increase in oxygen levels in the medium, which indicated a decrease in the respiratory activity of cells. In time, the phase of rapid decline in respiration coincided with the phase of decreased growth rate. In aerobic cultures of E. coli, respiratory activity is closely related to the generation of membrane potential. However, only a small, but statistically significant, decrease in membrane potential, measured using the fluorescent dye DiBAC4(3), was found with CBR-384. It is known that in aerobic E. coli cultures growing on sulfate as a sulfur source, stress-induced growth inhibition is accompanied by an increase in extracellular glutathione (GSH) and H2S export. The use of a sulfide-specific electrode revealed that when E. coli growth is stopped by CBR-384, sulfide is also exported into the medium. Under these conditions, an increase in extracellular GSH was also noted. The effect of CBR-386 on E. coli, assessed by these four parameters, was less pronounced. The differences in the biological activities of CBR-384 and CBR-386 may be due to differences in their structures.