Advances in Ciprofloxacin Derivatives: Emerging Strategies to Combat Antimicrobial Resistance

Antimicrobial resistance (AMR) is a worldwide health crisis challenging existing antibiotics, leading to increased mortality. Since their discovery in the early twentieth century, antibiotics have transformed medicine and saved countless lives. But today, the worrying increase in antibiotic resistance casts a shadow over the discovery of antibiotics. The abuse and overuse of antibiotics has led to the unrelenting adaptability of microbes, which is the cause of this global issue. With particular attention on ciprofloxacin (CIP), 2nd generation fluoroquinolones work by preventing DNA gyrase and topoisomerase IV from performing their vital functions, which include transcription, recombination, replication, and condensed DNA remodeling. Numerous researchers have developed CIP derivatives that are promising treatments, but factors such as overuse, multiple drug therapy, and misuse contribute to widespread resistance along with different side effects. So, to overcome such problems, diverse strategies to enhance CIP efficacy are examined, including synthetic approaches such as hybridization, Mannich reaction, and oxidation, aiming to modify the structure of CIP and create novel compounds with potentially enhanced biological activities, improved efficacy, or reduced side effects, which happens as a result of chemical and physical changes, typically involving one or more reactions. Along with this, nanotechnology for drug delivery and synergistic combinations with aminoglycosides, tobramycin, or azithromycin, antimicrobial peptides (AMPs) and monoclonal antibodies (mAbs) offer potential to combat multidrug-resistant strains. This review provides insights into potential breakthroughs necessary to overcome AMR challenges and advance effective emerging synthetic and delivery approaches for antibacterial treatments. Overall, we have compiled different emerging strategies to develop CIP derivatives with the aim of discovering new and more effective ways to combat drug-resistant infections.