19/03/2025 ore 14.00 Aula B (aulette Blu CU010) Prof. Antonio Coluccia, PhD Department of Chemistry and Technology of Drugs Sapienza University of Rome (Italy)
Antimicrobial resistance (AMR) is posing a major threat to human health globally. Approximately 5 million deaths were attributed to AMR in 2019 and this figure is predicted to worsen, reaching 10 million deaths by 2050. In the search for new compounds able to tackle AMR, FtsZ inhibitors represent a valuable option. In the present study, it is reported a structure-based virtual screening that led to the identification of derivative C11 endowed with an excellent MIC value of 2 μg/ml against Staphylococcus aureus. Biochemical assays clarified that compound C11 targets FtsZ by inhibiting its polymerization process. C11 also showed a notable antimicrobial activity against S. aureus cystic fibrosis isolates and MRSA strains. Derivative C11 did not show cytotoxicity while it had a synergistic effect with methicillin. C11 also showed an increase survival in the Galleria mellonella infection model. Lastly, structure-activity relationship and binding mode analyses were reported.
19 Marzo 2025