Development of novel seleno-ciprofloxacin derivatives: an X in the antibiotic treasure map

The growing emergence of pathogens resistant to the currently available antibacterial agents is an increasing and troublesome health problem worldwide. Modifying known active compounds has received wide attention and has become one of the hot spots in developing novel antibiotics. Herein we describe the synthesis of fifteen novel analogs of ciprofloxacin with a selenocyanate or selenoester functionality in the scaffold of this fluoroquinolone. Notably, these selenium (Se)-bearing molecules showcase an interesting antibacterial activity against eight different bacteria strains. Amidst them, CP7 had an important effect on the bacterial growth as observed in the growth kinetic studies carried out. Moreover, its efficacy to disrupt and prevent the formation of biofilms by Pseudomonas aeruginosa (P. aeruginosa) surpassed the one obtained with the parent antibiotic. Additionally, this ciprofloxacin analog demonstrated to have a potent inhibitory activity towards the DNA gyrase from Escherichia coli (E. coli) both in silico and in vitro.