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<p>This study reports the successful synthesis and design of a&#xa0;novel series of oxime-fused quinolone (pipemidic acid) hybrid analogues III (a–e)&#xa0;as potential antibacterial and anti-inflammatory agents. A panel of bacterial and fungal strains was used to evaluate the antibacterial activity of the synthesized compounds, while <i>COX-II</i> inhibition studies assessed their anti-inflammatory activity. Compound IIIc showed significant inhibition against <i>E. faecalis, S. aureus, E. coli</i>, and <i>P. aeruginosa</i>, with a minimum inhibitory concentration (MIC) of 9&#xa0;µg/mL (ZI 8-9&#xa0;mm), surpassing the parent drug, pipemidic acid (MIC 16&#xa0;µg/mL) (ZI 4-5&#xa0;mm) &amp; comparable to ciprofloxacin (MIC 0.5&#xa0;µg/mL). In contrast, against <i>Candida albicans</i>, the compounds demonstrated limited antifungal activity (MIC &gt; 512&#xa0;µg/mL) compared to fluconazole (MIC 2&#xa0;µg/mL). Structural elucidation was confirmed through FTIR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and mass spectrometry analyses. The oxime group was introduced at the C-2 position of the piperazine-linked quinolone (pipemidic acid) scaffold. Among the series, compound IIIb exhibited 40.7% inhibition of carrageenan-induced paw edema (<i>P</i> &lt; 0.001), similar to naproxen (40.0%). Molecular docking studies supported these findings, showing that compound IIIc displayed the strongest binding affinities (-10.3, -8.2, and -8.3&#xa0;kcal/mol) with key amino acid residues (ARG57, THR46, MET16, HIS45, VAL122) in the active sites of <i>DNA gyrase</i> from <i>S. aureus</i> (2w9s), <i>P. aeruginosa</i> (6m1j), and <i>E. coli</i> (6cqa), even outperforming reference ligands. These results suggest that oxime-derivatives of quinolone, especially IIIc, have strong potential as lead candidates for antibacterial and anti-inflammatory drug development.</p> Graphical abstract <p></p>

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Design, synthesis and biological evaluation of oxime derivatives of quinolone for antimicrobial and anti-inflammatory activities

  • 期刊论文

  • 发表日期：

    2026年7月19日

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  • Vishal Sharma,
  • Rina Das,
  • Diksha Sharma,
  • Dinesh Kumar Mehta

摘要

This study reports the successful synthesis and design of a novel series of oxime-fused quinolone (pipemidic acid) hybrid analogues III (a–e) as potential antibacterial and anti-inflammatory agents. A panel of bacterial and fungal strains was used to evaluate the antibacterial activity of the synthesized compounds, while COX-II inhibition studies assessed their anti-inflammatory activity. Compound IIIc showed significant inhibition against E. faecalis, S. aureus, E. coli, and P. aeruginosa, with a minimum inhibitory concentration (MIC) of 9 µg/mL (ZI 8-9 mm), surpassing the parent drug, pipemidic acid (MIC 16 µg/mL) (ZI 4-5 mm) & comparable to ciprofloxacin (MIC 0.5 µg/mL). In contrast, against Candida albicans, the compounds demonstrated limited antifungal activity (MIC > 512 µg/mL) compared to fluconazole (MIC 2 µg/mL). Structural elucidation was confirmed through FTIR, 1H NMR, 13C NMR, and mass spectrometry analyses. The oxime group was introduced at the C-2 position of the piperazine-linked quinolone (pipemidic acid) scaffold. Among the series, compound IIIb exhibited 40.7% inhibition of carrageenan-induced paw edema (P < 0.001), similar to naproxen (40.0%). Molecular docking studies supported these findings, showing that compound IIIc displayed the strongest binding affinities (-10.3, -8.2, and -8.3 kcal/mol) with key amino acid residues (ARG57, THR46, MET16, HIS45, VAL122) in the active sites of DNA gyrase from S. aureus (2w9s), P. aeruginosa (6m1j), and E. coli (6cqa), even outperforming reference ligands. These results suggest that oxime-derivatives of quinolone, especially IIIc, have strong potential as lead candidates for antibacterial and anti-inflammatory drug development.

Graphical abstract