Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug...

Area of Science:

• Medicinal Chemistry
• Computational Biology
• Antimicrobial Resistance

Background:

• Antibiotic resistance poses a significant global health challenge, necessitating the development of novel antibacterial agents.
• The World Health Organization has identified several Gram-negative pathogens as high-priority targets for new therapies.

Purpose of the Study:

• To evaluate the potential antibacterial activity of nine novel fluoroquinolone compounds against key resistant Gram-negative bacteria.
• To investigate the binding interactions of these compounds with DNA gyrase, a crucial target for antibacterial drugs.

Main Methods:

• In silico molecular docking and molecular dynamics (MD) simulations were employed.
• Wild-type (WT) and mutant-type (MT) DNA gyrases from target pathogens served as biological targets.
• Binding energies and interactions with quinolone resistance-determining regions (QRDR) were analyzed.

Main Results:

• Compound 9FQ exhibited the highest binding energy with *Escherichia coli* DNA gyrase in both docking and MD simulations.
• Compound 9FQ interacted with critical QRDR residues in GyrA and GyrB, potentially inhibiting DNA replication.
• Compound 1FQ also demonstrated favorable binding affinity to DNA gyrase.

Conclusions:

• Novel fluoroquinolone compounds, particularly 9FQ, show significant potential as antibacterial agents against Gram-negative pathogens.
• These in silico findings provide a strong foundation for further in vitro validation and the development of new antibiotics.