Bacterial riboflavin riboswitches

Ribocil-C is a highly selective inhibitor of the flavin mononucleotide (FMN) riboswitch that controls expression of de novo riboflavin (RF, vitamin B2) biosynthesis in Escherichia coli . Ribocil-C specifically inhibits dual FMN riboswitches, separately controlling RF biosynthesis and uptake processes essential for Staphylococcus aureus growth and pathogenesis. Ribocil-C is a small-molecule synthetic mimic of FMN that binds the FMN riboswitch of multiple GN bacteria, including Escherichia coli , Pseudomonas aeruginosa , and Acinetobacter baumannii , to inhibit ribB expression, RF synthesis, and consequently arrest bacterial growth.

Higher dose Ribocil-C treatment groups (60 and 120 mg kg21 ribocil-C) demonstrate a dose-dependent reduction in bacterial burden of 1.87 and 3.29 log ₁₀ [CFU per g spleen] reduction respectively versus shamtreated mice, without mortality or gross effects of toxicity observed.