Penicillin-binding protein (PBP) inhibitor development: A 10-year chemical perspective - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Experimental Biology and Medicine Année : 2023

Penicillin-binding protein (PBP) inhibitor development: A 10-year chemical perspective

Penicillin-binding protein (PBP) inhibitor development: A 10-year chemical perspective.

Résumé

Bacterial cell wall formation is essential for cellular survival and morphogenesis. The peptidoglycan (PG), a heteropolymer that surrounds the bacterial membrane, is a key component of the cell wall, and its multistep biosynthetic process is an attractive antibacterial development target. Penicillin-binding proteins (PBPs) are responsible for cross-linking PG stem peptides, and their central role in bacterial cell wall synthesis has made them the target of successful antibiotics, including β-lactams, that have been used worldwide for decades. Following the discovery of penicillin, several other compounds with antibiotic activity have been discovered and, since then, have saved millions of lives. However, since pathogens inevitably become resistant to antibiotics, the search for new active compounds is continuous. The present review highlights the ongoing development of inhibitors acting mainly in the transpeptidase domain of PBPs with potential therapeutic applications for the development of new antibiotic agents. Both the critical aspects of the strategy, design, and structure–activity relationships (SAR) are discussed, covering the main published articles over the last 10 years. Some of the molecules described display activities against main bacterial pathogens and could open avenues toward the development of new, efficient antibacterial drugs.

Dates et versions

hal-04510760 , version 1 (19-03-2024)

Identifiants

Citer

Ariane Bertonha, Caio Silva, Karina Shirakawa, Daniel Trindade, Andréa Dessen. Penicillin-binding protein (PBP) inhibitor development: A 10-year chemical perspective. Experimental Biology and Medicine, 2023, 248 (19), pp.1657-1670. ⟨10.1177/15353702231208407⟩. ⟨hal-04510760⟩
5 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More