Estimation of the activity of modified pyrimidine nucleoside derivatives on bacteria cells

Abstract

The increase in prevalence of antimicrobial-resistant bacteria (ARB) is currently a serious threat, thus there is a need for new classes antimicrobial compounds to combat infections caused by these ARB. The growth inhibition ability of derivatives of the components of nucleic acids has been well-characterized but not for its antimicrobial characteristics. It was found that modified nucleosides arabinofuranosylcytosine (cytarabine, ara-C), [1-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)- 4-(1,2,4-triazol-1-yl)]uracil (TTU), and nucleotides cytarabine-5′-monophosphate (ara-CMP), and O2,2′-cyclocytidine-5′- monophosphate (cyclocytidine monophosphate, cyclo-CMP) were able to inhibit Escherichia coli, Sarcina lutea, Bacillus cereus, and Proteus mirabilis strains in a time and dose dependent manner via killing kinetics assay. It was demonstrated that studied modified pyrimidine nucleosides derivatives enhanced the production of intracellular reactive oxygen species (ROS) over time (validated via DCFA-DA probe assay). This study has revealed the mechanism of action of cytarabine, cyclocytidine monophosphate, and TTU as an antimicrobial agent for the first time, and has shown that these pyrimidine derivatives enhanced might be able to combat infections caused by E. coli, S. lutea, B. cereus, and P. mirabilis in the future.