Scholarlink

<p>In this study we present a novel class of <i>N</i>-imidazopyridine (impy) derivatives (<b>12</b>–<b>15</b>) of noscapine by tethering the imidazo[1,2-a]pyridine core to the N-atom of the isoquinoline ring of the lead molecule noscapine. These derivatives were found to have better docking scores (− 6.213 to − 7.897 kcal/mol) than noscapine (− 4.960 kcal/mol). Further, the calculated binding energy ranged between − 25.85 to − 35.57 kcal/mol, as determined by MD simulations and MM-PBSA calculations. Tubulin binding assay also revealed higher binding affinity for compounds 12, 13, 14<b>,</b> and 15 with the equilibrium dissociation constant (<i>K</i><sub><i>D</i></sub>) value of 78 ± 3.8&#xa0;µM, 66 ± 1.7&#xa0;µM, 56 ± 1.8&#xa0;µM, and 35 ± 2.4&#xa0;µM, respectively. These derivatives also exhibited potent cytotoxicity against breast cancer cell lines (MCF-7 &amp; MDA-MB-231), with IC<sub>50</sub> values ranging from 3.7 to 32.4&#xa0;µM, without any toxicity to normal human embryonic kidney (HEK) cells (IC<sub>50</sub> value &gt; 1500&#xa0;µM). FACS analysis revealed early apoptotic (45%) and late apoptotic cells (35%) when treated with the <i>N</i>-imidazopyridine derivatives (<b>15</b>) and arrested the cell cycle at the G2/M phase. Moreover, the impy derivative <b>15</b> was found to reduce the volume of implanted tumor in nude mice using xenografts of MCF-7 cells without any severe toxicity. Thus, we can infer that <i>N</i>-imidazopyridine-noscapinoids have increased potential as anticancer agents.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

N-imidazopyridine derivatives of noscapine as potent tubulin-binding anticancer agents: chemical synthesis and cellular evaluation

  • 期刊论文

  • 发表日期：

    2025年6月25日

查看全文
  • Pooja Dash,
  • Pratyush Pragyandipta,
  • Srinivas Kantevari,
  • Pradeep Kumar Naik

摘要

In this study we present a novel class of N-imidazopyridine (impy) derivatives (12–15) of noscapine by tethering the imidazo[1,2-a]pyridine core to the N-atom of the isoquinoline ring of the lead molecule noscapine. These derivatives were found to have better docking scores (− 6.213 to − 7.897 kcal/mol) than noscapine (− 4.960 kcal/mol). Further, the calculated binding energy ranged between − 25.85 to − 35.57 kcal/mol, as determined by MD simulations and MM-PBSA calculations. Tubulin binding assay also revealed higher binding affinity for compounds 12, 13, 14, and 15 with the equilibrium dissociation constant (KD) value of 78 ± 3.8 µM, 66 ± 1.7 µM, 56 ± 1.8 µM, and 35 ± 2.4 µM, respectively. These derivatives also exhibited potent cytotoxicity against breast cancer cell lines (MCF-7 & MDA-MB-231), with IC50 values ranging from 3.7 to 32.4 µM, without any toxicity to normal human embryonic kidney (HEK) cells (IC50 value > 1500 µM). FACS analysis revealed early apoptotic (45%) and late apoptotic cells (35%) when treated with the N-imidazopyridine derivatives (15) and arrested the cell cycle at the G2/M phase. Moreover, the impy derivative 15 was found to reduce the volume of implanted tumor in nude mice using xenografts of MCF-7 cells without any severe toxicity. Thus, we can infer that N-imidazopyridine-noscapinoids have increased potential as anticancer agents.