Synthesis of a di-O-acylated deoxynojirimycin (DNJ) derivative and evaluation of its antibacterial and antibiofilm activity against Staphylococcus aureus and Stenotrophomonas maltophilia

Herein we report the synthesis of a novel di-O-acylated DNJ derivative, conceived to study whether iminosugar derivatization with a lipophilic acyl moiety could positively affect its antibacterial properties. The well-known PS-TPP/I2/ImH activating system was used to readily install the acyl chains on the iminosugar, leading to the desired compound in high yield. Biological assays revealed that a di-O-lauroyl DNJ derivative enhanced the antibacterial effect of gentamicin and amikacin against S. aureus and S. maltophilia strains, respectively, suggesting a potential role as antibiotic adjuvant. Furthermore, even though this compound displayed only a weak concentration-dependent inhibitory effect on biofilm formation in S. aureus, it was able to significantly reduce the viability of S. aureus and S. maltophilia preformed biofilms. The results confirm the antibacterial potential of piperidine iminosugars and open the way to further studies involving novel lipophilic derivatives to optimize the antibacterial adjuvant effect herein observed for iminosugar 12.