Assessing the Potential of N-Butyl-l-deoxynojirimycin (l-NBDNJ) in Models of Cystic Fibrosis as a Promising Antibacterial Agent

Over the past few years, L-iminosugars have revealedattractive pharmacological properties for managing rare diseasesincluding Cystic Fibrosis (CF). The iminosugar N-butyl-L-deoxynojirimycin (L-NBDNJ, ent-1), prepared by a carbohydrate-based route, was herein evaluated for its anti-inflammatory andanti-infective potential in models of CF lung disease infection. Asignificant decrease in the bacterial load in the airways wasobserved in the murine model of Pseudomonas aeruginosa chronicinfection in the presence of L-NBDNJ, also accompanied by amodest reduction of inflammatory cells. Mechanistic insights intothe observed activity revealed that L-NBDNJ interferes with theexpression of proteins regulating cytoskeleton assembly andorganization of the host cell, downregulates the main virulencefactors of P. aeruginosa involved in the host response, and affects pathogen adhesion to human cells. These findings along with theobservation of the absence of an in vitro bacteriostatic/bactericidal action of L-NBDNJ suggest the potential use of this glycomimeticas an antivirulence agent in the management of CF lung disease.