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<p>This study used a nano-synergistic approach to augment the potency of ceftibuten by preparing a nano-formulation of ceftibuten. We also added a carbonitrile based molecule (ID: MCULE-1352214421–0-56) as a synergizer. A one-pot synthesis was performed to prepare CFB-AuNPs (i.e., ceftibuten-loaded gold nanoparticles), wherein ceftibuten played the role of reduction as well as capping molecule. The CFB-AuNPs were characterized with the aid of spectrometry, dynamic light scattering (DLS)-based zeta size and zeta potential measurements, and also by transmission electron microscopy (TEM). Additionally, evaluation of activity of ceftibuten (alone), CFB-AuNPs, and their combination with the synergizer was performed on resistant <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> bacterial isolates. YASARA-docking was used to investigate possible binding interactions of the synergizer with important antibiotic resistance enzymes found in bacteria, namely, CTX-M, KPC and SHV. Molecular dynamics simulation was performed for SHV-synergizer complex. UV-spectra displayed peak of AuNPs at 523 nm, while TEM-based size was measured as 12–25 nm. The effective MIC<sub>50</sub>s of ceftibuten-loaded AuNPs were decreased by more than 50%. Addition of the synergizer augmented this activity, with MIC<sub>50</sub> values declining to 3.76 ± 0.8 µg/mL and 2.98 ± 0.7 µg/mL for <i>E. coli</i> and <i>K. pneumoniae</i> test strains, respectively. Hence, the combination of CFB-AuNPs and the ligand (ID: MCULE1352214421056) was determined to be highly potent. Docking studies revealed significant interaction of the synergizer with the aforementioned bacterial enzymes. Molecular dynamics simulation confirmed the stability of SHV-synergizer complex. Overall, the results indicated that apart from acting as a synergizer in the described gold nanoparticle coupled antibiotic system, the small molecule (ID: 1,352,214,421,056) stored in the mcule.com database could be capable of thwarting the antibiotic resistance in bacteria by several plausible biomolecular interactions. As our current antibiotic stockpile continues to be challenged by hardier bacteria, the importance of the present study in relation to antibiotic resistance is understandable.</p>

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A Novel Synergized Nanoformulation Revives the Activity of Ineffective Ceftibuten Antibiotic: Synthesis, Characterization, In Vitro Validation and Molecular Interactions Study

  • 期刊论文

  • 发表日期：

    2025年5月29日

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  • Shazi Shakil,
  • Syed M. Danish Rizvi,
  • Mohd Rehan,
  • Syed Kashif Zaidi,
  • Shams Tabrez,
  • Mohd Suhail,
  • Nigel H. Greig

摘要

This study used a nano-synergistic approach to augment the potency of ceftibuten by preparing a nano-formulation of ceftibuten. We also added a carbonitrile based molecule (ID: MCULE-1352214421–0-56) as a synergizer. A one-pot synthesis was performed to prepare CFB-AuNPs (i.e., ceftibuten-loaded gold nanoparticles), wherein ceftibuten played the role of reduction as well as capping molecule. The CFB-AuNPs were characterized with the aid of spectrometry, dynamic light scattering (DLS)-based zeta size and zeta potential measurements, and also by transmission electron microscopy (TEM). Additionally, evaluation of activity of ceftibuten (alone), CFB-AuNPs, and their combination with the synergizer was performed on resistant Escherichia coli and Klebsiella pneumoniae bacterial isolates. YASARA-docking was used to investigate possible binding interactions of the synergizer with important antibiotic resistance enzymes found in bacteria, namely, CTX-M, KPC and SHV. Molecular dynamics simulation was performed for SHV-synergizer complex. UV-spectra displayed peak of AuNPs at 523 nm, while TEM-based size was measured as 12–25 nm. The effective MIC50s of ceftibuten-loaded AuNPs were decreased by more than 50%. Addition of the synergizer augmented this activity, with MIC50 values declining to 3.76 ± 0.8 µg/mL and 2.98 ± 0.7 µg/mL for E. coli and K. pneumoniae test strains, respectively. Hence, the combination of CFB-AuNPs and the ligand (ID: MCULE1352214421056) was determined to be highly potent. Docking studies revealed significant interaction of the synergizer with the aforementioned bacterial enzymes. Molecular dynamics simulation confirmed the stability of SHV-synergizer complex. Overall, the results indicated that apart from acting as a synergizer in the described gold nanoparticle coupled antibiotic system, the small molecule (ID: 1,352,214,421,056) stored in the mcule.com database could be capable of thwarting the antibiotic resistance in bacteria by several plausible biomolecular interactions. As our current antibiotic stockpile continues to be challenged by hardier bacteria, the importance of the present study in relation to antibiotic resistance is understandable.