مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Molecular Docking Discovery of Potent Klebsiella aerogenes Urease Inhibitors: Acetyl(sulfanyloxy)azanium vs. N-Methoxyacetamide
Molecular Docking Discovery of Potent Klebsiella aerogenes Urease Inhibitors: Acetyl(sulfanyloxy)azanium vs. N-Methoxyacetamide
Haniyeh Soleymani,1Elnaz Afshari,2,*
1. Department of Microbiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran. 2. Department of Microbiology and Microbial Biotechnology, Biological Science and Technology Branch, Shahid Beheshti University, Tehran, Iran. Department of Microbiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
Introduction: Klebsiella aerogenes is a notable pathogen responsible for severe hospital-acquired urinary tract infections and surgical site infections, increasingly complicated by its ability to develop antibiotic resistance, making treatment challenging. New promising strategy for prevention of klebsiella infection is screening of new inhibitors against bacterial virulence factors. Therefore, this study targets the urease enzyme, critical virulence factor for pathogen’s physiology of klebsiella, to evaluate and compare the potential of two anti-urease candidates via molecular docking analysis.
Methods: The 3D structure of Urease of Klebsiella (PDB ID: 1FWJ) and its inhibitory ligands, Acetyl (sulfanyloxy)azanium (PubChem CID: 173416439) and N-Methoxyacetamide (PubChem CID: 138591) were obtained from the RCSB PDB and PubChem databases, respectively. Protein and ligands were prepared and docked using Molegro Virtual Docker6.0. The best interaction with the lowest binding energy was analyzed via Molegro Molecular Viewer. Finally, pharmacokinetic properties were investigated using SwissADME server.
Results: Molecular docking analysis revealed that Acetyl(sulfanyloxy)azanium exhibited a significantly higher binding affinity to urease residues compare to N-Methoxyacetamide (–46 vs. –42 kcal/mol). The interaction profile of Acetyl(sulfanyloxy)azanium (Molecular weight: 108.14g/mol) included five steric interactions (with Ala445, Tyr473, Ser436, Lys443 and Pro444), five hydrogen bonds (with Lys4343 Tyr473, Pro444, Tyr473,and Lys443 residues), surpassing N-Methoxyacetamide’s one steric interaction and one hydrogen bond with lys443. ADME profiling further indicated that Acetyl(sulfanyloxy)azanium possesses better water solubility (LogS:–0.42 vs. 0), lower lipophilicity (LogP:0 vs. 0.89), and higher polarity (TPSA:81.71Ų vs. 38.33Ų), making it more suitable for drug development than N-Methoxyacetamide (Molecular weight: 89.09g/mol). Overall, Acetyl(sulfanyloxy)azanium demonstrated a more favorable pharmacological profile compared to N-Methoxyacetamide, indicating its potential as a better lead compound for drug development. Both compounds comply well with Lipinski's rules for drug-likeness.
Conclusion: Our findings showed that Acetyl(sulfanyloxy)azanium is a more promising inhibitor of Klebsiella aerogenes urease compared to N-Methoxyacetamide. Further in vitro and in vivo studies are necessary to validate their therapeutic potential.