Synthesis and Evaluation of Persulfide-Cleavable Fluorogenic Probes

Abstract

Antibiotic resistance is a global issue that directly increases the risks associated with bacterial infections. Hydrogen sulfide (H 2 S) and polysulfides (RS n H) are reactive sulfur species produced by the bacteria during antibiotic-induced stress. Among these, persulfides (RSSH) have a unique reactivity, functioning as nucleophiles and electrophiles. Herein, we propose to develop a persulfide-activated antibiotic prodrug for antibacterial studies. As a proof of concept, fluorophore was initially attached via ester linkage and made compound 3. The fluorescence response of 3 towards Na 2 S 4 was monitored in the buffer. Additionally, the stability and selectivity of 3 were monitored. The attachment of fluorophore via amide linkage and the validation are in progress. After evaluation, an antibiotic (moxifloxacin) will be appended to it, and its effect on antibiotic resistance will be studied. Further, this strategy can be extended to release antibiotics and evaluate its therapeutic potential.