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<p>Cancer remains the second leading cause of mortality globally, necessitating the development of novel therapeutic agents. In this work, we synthesized 34 derivatives of nitrated <i>N</i>-substituted-4-hydroxy-2-quinolone-3-carboxamides, which were spectroscopically analyzed using FT-IR, NMR (<sup>1</sup>H and <sup>13</sup>C), and elemental analysis. Derivatives tailored with <i>m</i>-CF<sub>3</sub> (<b>10</b>), <i>m</i>-OCH<sub>3</sub> (<b>13</b>), <i>m</i>-Cl (<b>16</b>), and <i>m</i>-F (<b>20</b>) benzyl moiety exhibited distinctive cytotoxicity against human colon cancer (HCT-116) cells with IC<sub>50s</sub> of 23.41, 27.14, 28.43, and 22.95 µM. Analogue <b>11</b> showed 100% inhibitory activity against ovarian cancer (NCI/ADR-RES), colon cancer (COLO 205), CNS cancer (SF-295), and melanoma (SK-MEL-2) cells. Cheminformatics analysis further revealed insights into the physicochemical and drug-like properties of these analogues, highlighting their potential to bind PI3Kα through alignment with key pharmacophoric features required for effective enzyme interaction. Molecular docking studies against both wild-type and mutant PI3Kα elucidated binding interactions, suggesting that specific substituents enhance selectivity and potency. This study highlights the therapeutic potential of quinolone derivatives in targeting cancer-related pathways and contributes valuable data to the ongoing search for more effective anticancer therapies.</p>

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Exploring the anticancer potential of nitrated N-substituted-4-hydroxy-2-quinolone-3-carboxamides: synthesis, biological assessment, and computational analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月22日

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  • Reem A. Islim,
  • Nisreen S. Hamadeh,
  • Reema Abu Khalaf,
  • Rima Hajjo,
  • Sanaa K. Bardaweel,
  • Kamal Sweidan,
  • Aya M. Al-Zuheiri,
  • Swapnaa Balaji,
  • Amit K. Tiwari,
  • Ghassan Abushaikha,
  • Dima A. Sabbah

摘要

Cancer remains the second leading cause of mortality globally, necessitating the development of novel therapeutic agents. In this work, we synthesized 34 derivatives of nitrated N-substituted-4-hydroxy-2-quinolone-3-carboxamides, which were spectroscopically analyzed using FT-IR, NMR (1H and 13C), and elemental analysis. Derivatives tailored with m-CF3 (10), m-OCH3 (13), m-Cl (16), and m-F (20) benzyl moiety exhibited distinctive cytotoxicity against human colon cancer (HCT-116) cells with IC50s of 23.41, 27.14, 28.43, and 22.95 µM. Analogue 11 showed 100% inhibitory activity against ovarian cancer (NCI/ADR-RES), colon cancer (COLO 205), CNS cancer (SF-295), and melanoma (SK-MEL-2) cells. Cheminformatics analysis further revealed insights into the physicochemical and drug-like properties of these analogues, highlighting their potential to bind PI3Kα through alignment with key pharmacophoric features required for effective enzyme interaction. Molecular docking studies against both wild-type and mutant PI3Kα elucidated binding interactions, suggesting that specific substituents enhance selectivity and potency. This study highlights the therapeutic potential of quinolone derivatives in targeting cancer-related pathways and contributes valuable data to the ongoing search for more effective anticancer therapies.