Exploring the potential role of GyrA inhibiting quinoline analog: an in silico study
Abstract
Fluoroquinolone-resistant Pseudomonas aeruginosa poses a significant global health concern, particularly in healthcare settings. This opportunistic pathogen has developed resistance against multiple classes of antibiotics, rendering infections challenging to treat. The present study focused on identifying quinoline analogs as potential inhibitors of gyrA in fluoroquinolone-resistant P. aeruginosa. Utilizing structural bioinformatics, molecular docking, molecular dynamics (MD) simulations, and MM/PBSA binding energy analyses, the quinoline analog, N-benzylquinoline-8-sulfonamide (M2), emerged as the most promising candidate. Molecular docking revealed M2’s better binding affinity to gyrA wild type as well as frequently observed mutants, demonstrated average binding energy of − 8.14 kcal/mol, significantly better than ciprofloxacin (− 7.13 kcal/mol) and levofloxacin (− 6.57 kcal/mol). M2 exhibited a robust inhibition constant of 1.09 µM, surpassing control antibiotics ciprofloxacin (6.11 µM) and levofloxacin (15.34 µM). MD simulations validated the dynamic stability of M2 and gyrA complexes (wild-type and mutant), whereas MM/PBSA analysis confirmed strong binding energetics. Principal Component Analysis (PCA) further validated the stability of these complexes by identifying the global energy minima across conformational landscapes. M2 exhibited enhanced efficacy and stability against resistance-associated mutations compared to the standard antibiotics ciprofloxacin and…
Read the paper
Related studies
- Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
- Photochemical behavior of levofloxacin
- Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose/ Fluid Volume Ratio
- Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides
- Synthesis of [11C]levofloxacin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.