Headway in Synthetic Chemistry: A Gateway for Antimicrobial Trojan Horse Strategy for Drug Repurposing Against...

Pseudomonas aeruginosa is a major cause of nosocomial infection which at times causes a grim situation in clinical setups. There is a dire need to develop strategies to overcome the increasing incidence of drug resistance in this organism. The protective outer membrane and over expressed efflux pumps serve as a major survival weapon for this pathogen, making it to resist present day antibiotics. The present review dwells on some of these strategies, with emphasis on tagging to existing antibiotics with siderophore as a carrier employing a Trojan horse strategy so that an antibiotic can creep into bacterial cell through the iron acquisition pathway. These hybrid drugs, defined as synthetic structures are likely to overcome drug resistance due to their ability to evade resistance mediated by multiple antibiotic resistance operon. The advances and challenges of siderophore-antibiotic conjugates are elaborated in this article. Moreover, several xeno-siderophore-antibiotic conjugates, currently in clinical trials, have been discussed. The present review provides insights into repurposing of fluroquinolones through siderophore targeted delivery to increase the biological activity of antibiotics. In the near future, siderophore-based Trojan horse antibiotics indeed will not only help in altering the potency of antibiotics, hence decreasing antimicrobial resistance, but also will lead to disarming the pathogen of its virulence.