In the field of medicinal chemistry, significant research efforts are dedicated to developing new antibiotics targeting clinically validated enzymes such as DNA gyrase and topoisomerase IV, which are crucial for bacterial DNA replication. Among the frontline classes of agents against broad-spectrum bacterial infections, quinolines and their analogues are particularly effective in inhibiting both targets [1]. However, the recent emergence of resistance, due to mutations that impair drug accumulation in bacterial cells and target recognition, has driven the development of new approaches for discovering innovative inhibitors. Drawing on our experience in the synthesis of quinoline-based compounds, we have focused on the study of piperazinylquinoline derivatives with potential antibiotic activity [2]. Induced Fit Docking (IFD) studies were performed on the DNA gyrase of S. aureus (PDB code 6FM4), to assess protein-ligand interactions between our molecular dataset and the target binding sites. The 6,7-dimethoxy-4-piperazinylquinoline compounds 1a-k (Figure 1) showed remarkable binding affinity to the DNA gyrase comparable to that of the reference ligand. The selected molecules were synthesized using appropriate synthetic strategies and characterized spectroscopically. Preliminary antibacterial tests showed promising activity of piperazinyl quinolines against S. aureus, known for its resistance to many conventional antibiotic therapies. Further in vitro studies are currently underway to elucidate the mechanism of action and validate the efficacy and therapeutic potential of these compounds.

Federica Alamia, G.L.M. (2024). Novel 6,7-dimethoxy-4-piperazinylquinoline derivatives as promising antibacterial agents against Staphylococcus aureus. In C.B. I. Arduino (a cura di), Proceedings of the Merck Young Chemists’ Symposium XXIII edition (pp. 165-165).

Novel 6,7-dimethoxy-4-piperazinylquinoline derivatives as promising antibacterial agents against Staphylococcus aureus

Federica Alamia
Primo
;
Gabriele La Monica;Alessia Bono;Antonino Lauria;Rosa Alduina;Annamaria Gallo;Annamaria MARTORANA
Ultimo
2024-01-01

Abstract

In the field of medicinal chemistry, significant research efforts are dedicated to developing new antibiotics targeting clinically validated enzymes such as DNA gyrase and topoisomerase IV, which are crucial for bacterial DNA replication. Among the frontline classes of agents against broad-spectrum bacterial infections, quinolines and their analogues are particularly effective in inhibiting both targets [1]. However, the recent emergence of resistance, due to mutations that impair drug accumulation in bacterial cells and target recognition, has driven the development of new approaches for discovering innovative inhibitors. Drawing on our experience in the synthesis of quinoline-based compounds, we have focused on the study of piperazinylquinoline derivatives with potential antibiotic activity [2]. Induced Fit Docking (IFD) studies were performed on the DNA gyrase of S. aureus (PDB code 6FM4), to assess protein-ligand interactions between our molecular dataset and the target binding sites. The 6,7-dimethoxy-4-piperazinylquinoline compounds 1a-k (Figure 1) showed remarkable binding affinity to the DNA gyrase comparable to that of the reference ligand. The selected molecules were synthesized using appropriate synthetic strategies and characterized spectroscopically. Preliminary antibacterial tests showed promising activity of piperazinyl quinolines against S. aureus, known for its resistance to many conventional antibiotic therapies. Further in vitro studies are currently underway to elucidate the mechanism of action and validate the efficacy and therapeutic potential of these compounds.
2024
Settore CHEM-07/A - Chimica farmaceutica
978-88-94952-50-6
Federica Alamia, G.L.M. (2024). Novel 6,7-dimethoxy-4-piperazinylquinoline derivatives as promising antibacterial agents against Staphylococcus aureus. In C.B. I. Arduino (a cura di), Proceedings of the Merck Young Chemists’ Symposium XXIII edition (pp. 165-165).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/670905
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