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<p>Pharmaceutical compounds are increasingly being released into the environment from various sources, with limited understanding of their impact on human health and ecosystems. Potential by-products of antibiotics, generated through different degradation pathways, may exhibit distinct kinetics, reactivity, and mechanisms, contributing to biotoxicity and antibacterial resistance. In this study, major degradants of ciprofloxacin (CIP) have been optimized geometrically using density functional theory with the B3LYP/6-31G + (d,p) basis set, and their thermal stability, chemical reactivity, spectral analysis, pharmacokinetics, and toxicological properties have been evaluated. Molecular docking and dynamic simulation analysis were performed against DNA gyrase and glucosamine-6-phosphate synthase to assess the binding strength and stability. In thermodynamic analysis, all the degradants indicated their thermal stability, and most of the degradants, including CIP11, exhibited the minimal HOMO–LUMO energy gap, suggesting improved chemical reactivity and bioactivity in molecular orbital data. The study also revealed that CIP2, CIP10, CIP11, and CIP16 exhibited higher binding affinity than the parent compound CIP. In ADMET, most of the degradants exhibited good human intestinal absorption except CIP10. All the compounds were found to be highly toxic to fish, and most of the degradants were AMES positive, indicating their mutagenic nature. So, their release into the environment untreated may endanger the ecosystem. The molecular dynamics simulation study demonstrated superior stability and compactness of the CIP2-2VF5 complex. Our study provides crucial insights into potential medicinal and toxicological properties of CIP and its degradants and suggests CIP2 and CIP11 as promising antimicrobial candidates for further investigation.</p> Graphical Abstract <p></p>

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Unveiling the structural, medicinal, and toxicological potential of ciprofloxacin and its major degradation products: a DFT and in-silico approach

  • 期刊论文

  • 发表日期：

    2025年11月20日

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  • Md. Okibur Rahman,
  • Suchana Rani Saha,
  • Md. Sakib Abdullah,
  • Mehedi Hasan,
  • Anita Ahona Protiva,
  • IV Hassan Siddique,
  • Monir Uzzaman,
  • Bakul Akter

摘要

Pharmaceutical compounds are increasingly being released into the environment from various sources, with limited understanding of their impact on human health and ecosystems. Potential by-products of antibiotics, generated through different degradation pathways, may exhibit distinct kinetics, reactivity, and mechanisms, contributing to biotoxicity and antibacterial resistance. In this study, major degradants of ciprofloxacin (CIP) have been optimized geometrically using density functional theory with the B3LYP/6-31G + (d,p) basis set, and their thermal stability, chemical reactivity, spectral analysis, pharmacokinetics, and toxicological properties have been evaluated. Molecular docking and dynamic simulation analysis were performed against DNA gyrase and glucosamine-6-phosphate synthase to assess the binding strength and stability. In thermodynamic analysis, all the degradants indicated their thermal stability, and most of the degradants, including CIP11, exhibited the minimal HOMO–LUMO energy gap, suggesting improved chemical reactivity and bioactivity in molecular orbital data. The study also revealed that CIP2, CIP10, CIP11, and CIP16 exhibited higher binding affinity than the parent compound CIP. In ADMET, most of the degradants exhibited good human intestinal absorption except CIP10. All the compounds were found to be highly toxic to fish, and most of the degradants were AMES positive, indicating their mutagenic nature. So, their release into the environment untreated may endanger the ecosystem. The molecular dynamics simulation study demonstrated superior stability and compactness of the CIP2-2VF5 complex. Our study provides crucial insights into potential medicinal and toxicological properties of CIP and its degradants and suggests CIP2 and CIP11 as promising antimicrobial candidates for further investigation.

Graphical Abstract