Design and evaluation of the bactericidal activity of new hydroxamic acid and hydrazide derivatives against mature S. aureus biofilms.

Bacterial biofilms represent a major clinical challenge due to their high tolerance to conventional antibiotics and their implication in persistent infections. Staphylococcus aureus is particularly known for its ability to form biofilms that significantly reduce antibiotic efficacy. In this context, the development of new molecules capable of eradicating mature biofilms is of great interest. Herein, we report the synthesis of 20 novel hydroxamic acid and hydrazide containing-imidazole compounds and the evaluation of their antibacterial effect on a panel of bacteria from the ESKAPE group including Staphylococcus aureus. The best identified compounds have been then screened for their capacity to eradicate S. aureus embedded in biofilm and highlighted compound 4e as a hit compound. Overall, this work provides a first-step evaluation of new hydroxamic acid and hydrazide derivatives, serving as a starting point for further pharmacomodulation and optimization to improve their pharmacokinetics and toxicological profiles.