Sarafloxacin

Sarafloxacin Full Name

Sarafloxacin

Sarafloxacin Introduction

Sarafloxacin is a synthetic fluoroquinolone antibiotic that exerts potent antibacterial activity by inhibiting topoisomerase II (DNA gyrase), an enzyme essential for bacterial DNA replication. As a typical member of the fluoroquinolone class, sarafloxacin holds significant importance in veterinary medicine, with an antibacterial spectrum covering a wide range of common pathogenic bacteria.

Sarafloxacin functions by binding to two key enzymes inside bacterial cells: DNA gyrase and topoisomerase IV. These enzymes are critical for bacterial DNA replication and transcription, as they modify the supercoiling state of DNA, allowing DNA strands to unwind and proceed with these processes. Sarafloxacin inserts into the transient intermediate formed when these enzymes cut the DNA, blocking the step where the enzyme re-ligates the DNA strands. This results in permanent breaks in the DNA strands. Such interference causes the collapse of the bacterial DNA replication fork, leading to fatal double-strand breaks in the DNA and ultimately triggering bacterial cell death.

Bacterial resistance to sarafloxacin primarily arises through target-site mutations and active efflux pumps. Point mutations can occur within the quinolone resistance-determining region (QRDR) of genes encoding DNA gyrase and topoisomerase IV (mainly gyrA and parC). These mutations alter the amino acid sequence of the enzymes, making it difficult for the drug to bind to its target, thereby conferring resistance. On the other hand, bacteria may overexpress efflux pumps (such as those from the RND family), which actively pump the drug out of the cell, reducing its intracellular concentration. Additionally, plasmid-mediated quinolone resistance (PMQR) genes are another contributing factor to resistance. In the treatment of related diseases, sarafloxacin is primarily effective against infections caused by susceptible bacteria. Studies have confirmed its good clinical efficacy against diseases caused by avian pathogenic Escherichia coli, such as colisepticemia in poultry.

Figure 1. The mechanism of L-leucine promoting the killing effect of sarafloxacin on drug-resistant Salmonella. (Source: Yang H, et al. 2023)

Alternate Names for Sarafloxacin

Sarafloxacin

• 1. Asadipour A, et al. N-substituted piperazinyl sarafloxacin derivatives: synthesis and in vitro antibacterial evaluation. Daru. 2018 Dec;26(2):199-207.
  2. Yang H, et al. L-leucine increases the sensitivity of drug-resistant Salmonella to sarafloxacin by stimulating central carbon metabolism and increasing intracellular reactive oxygen species level. Front Microbiol. 2023 May 12;14:1186841.