Florfenicol-Polyarginine Conjugates Exhibit Promising Antibacterial Activity Against Resistant Strains

Abstract

Florfenicol was widely used as antibiotic in the livestock and poultry breeding industry, resulting in a serious problem of drug resistance. In order to solve the resistance of florfenicol, this study designed and synthesized a new series of florfenicol-polyarginine conjugates and tested for antimicrobial activities. Drug-sensitive bacteria, gram-negative bacteria Escherichia coli (E. coli) and gram-positive Staphylococcus aureus (S. aureus), were sensitive to several of the compounds tested. These conjugates also showed excellent activity against drug-resistant strains such as methicillin-resistant S. aureus (MRSA) and florfenicol resistant Escherichia coli strains (2017XJ30, 2019XJ20), one of which as E6 had a minimum inhibitory concentration of 12.5 μmol/L. These conjugates did not allow bacteria to develop resistance and also decreased bacterial growth by membrane depolarization and disruption. Additionally, florfenicol succinate (C1) showed certain activity after coupling with arginine. This suggested that conjugating arginine to florfenicol succinate effectively modulated the properties of prodrugs. These new conjugates may provide useful insights for expanding the pool of antibiotics.

Antibacterial Prodrugs to Overcome Bacterial Antimicrobial Resistance

“…Florfenicol, belonging to the phenicol family of antibiotics, displays a broad antibacterial spectrum and good efficiency; however, its application is limited by its poor water-solubility [ 4 , 48 ]. Li et al [ 48 ] developed a new set of florfenicol–polyarginine conjugates with selective toxicity towards bacterial cells when compared to mammalian cells, showing antibacterial activity in serum and plasma.…”

“…Florfenicol, belonging to the phenicol family of antibiotics, displays a broad antibacterial spectrum and good efficiency; however, its application is limited by its poor water-solubility [ 4 , 48 ]. Li et al [ 48 ] developed a new set of florfenicol–polyarginine conjugates with selective toxicity towards bacterial cells when compared to mammalian cells, showing antibacterial activity in serum and plasma. Moreover, these conjugates, especially 65 – 67 ( Figure 20 ), demonstrated excellent activity against MRSA and florfenicol-resistant E. coli , with MIC values of 12.5 µM against both strains, being able to decrease bacterial growth through membrane depolarization and disruption.…”

Design and Synthesis of Novel Antimicrobial Agents

“…Cell-penetrating peptides (CPPs), such as polyarginine, permeate the membranes of microbial cells to suppress bacteria. A brand-new family of florfenicol-polyarginine conjugates was created by Li et al [ 248 ]. The peptide-florfenicol conjugates were created by esterifying the hydroxyl group of florfenicol with succinic, glutaric, and hexanedioic anhydrides, followed by amidation with Argi-nine polypeptide.…”

Study on the Direct and Indirect Photolysis of Antibacterial Florfenicol in Water Using DFT/TDDFT Method and Comparison of Its Reactivity with Hydroxyl Radical under the Effect of Metal Ions

“…Florfenicol (FLO) is a broad-spectrum chloramphenicol antibiotic widely used in the prevention and treatment of bacterial diseases, which can inhibit or eliminate the growth of microorganisms [ 1 , 2 , 3 , 4 , 5 ]. During aquaculture, FLO, as a pharmaceutical feed, is usually leached directly or released into the aquatic environment with feces [ 6 , 7 ].…”