Design, synthesis, in vitro biological evaluation and anti-biofilm activity of new beta-lactam and linezolid-like compounds as potential antibacterial agents against Staphylococcus aureus infections in cystic fibrosis patients

In view of the widespread problem of antibiotic-resistance, innovative antibacterial strategies are required to improve the clinical outcome in CF infections. This project aims to develop new potential therapeutic alternatives for the treatment of respiratory staphylococcal infections in CF patients. New anti-staphylococcal compounds, with beta-lactam or oxazolidinones-like structures, will be developed. The multidisciplinary approach of this project will involve the Unit of Milano isolating and characterising strains of S. aureus which will be used for screening libraries of compounds developed by the Bologna Unit during the first part of the project. Lead compounds will be optimized on the basis of antibacterial activity assessed by Milano-Bicocca Unit; lead compounds and their chemical modifications will be also be further analysed. Finally electron microscopy and cytotoxicity studies will also be carried out to determine their possible mechanism of action of the most promising compounds. The goal of this research is the development of new lead compounds active against antibiotic-resistant strains of Staphylococcus aureus within the two years duration of the project.