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<p>Cancer remains a major global health challenge, necessitating the development of novel targeted treatments. Herein, a series of quinoline-based pyrazoline molecules containing different heterocyclic substitutions were designed, synthesized, and evaluated as potential EGFR-targeted anticancer agents. FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometric analysis were used to analyze the synthesized compounds. The antiproliferative activity of the derivatives was assessed against human breast cancer (MDA-MB-231) and ovarian cancer (SK-OV-3) cell lines using in vitro assays. Among the synthesized compounds, PBc1 exhibited the greatest in vitro antiproliferative activity against both MDA-MB-231 and SK-OV-3 cell lines. ELISA-based assessment showed reduced EGFR phosphorylation after PBc1 treatment, suggesting a possible EGFR-associated mechanism of action. Furthermore, DAPI-stained confocal microscopy revealed nuclear morphological changes, including chromatin condensation, nuclear fragmentation, and membrane blebbing, consistent with apoptosis-associated features. Molecular docking studies against wild-type (1M17) and mutant EGFR (4ZAU) showed favorable binding interactions with key active-site residues. Molecular dynamics simulations further confirmed the stability of the PBc1–protein complexes throughout the simulation period. In silico ADMET studies predicted favorable pharmacokinetic and toxicity profiles for the synthesized derivatives. Overall, the integrated experimental and computational findings suggest that PBc1 is a promising compound for further biological and mechanistic investigation.</p> Graphical abstract <p></p>

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Design, synthesis, antiproliferative evaluation, and computational studies of novel quinoline–pyrazoline hybrids against breast and ovarian cancer cell lines

  • 期刊论文

  • 发表日期：

    2026年7月19日

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  • Prachita Gauns Dessai,
  • Parixit Bhandurge,
  • Celina Nazareth,
  • Sahili Naik

摘要

Cancer remains a major global health challenge, necessitating the development of novel targeted treatments. Herein, a series of quinoline-based pyrazoline molecules containing different heterocyclic substitutions were designed, synthesized, and evaluated as potential EGFR-targeted anticancer agents. FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometric analysis were used to analyze the synthesized compounds. The antiproliferative activity of the derivatives was assessed against human breast cancer (MDA-MB-231) and ovarian cancer (SK-OV-3) cell lines using in vitro assays. Among the synthesized compounds, PBc1 exhibited the greatest in vitro antiproliferative activity against both MDA-MB-231 and SK-OV-3 cell lines. ELISA-based assessment showed reduced EGFR phosphorylation after PBc1 treatment, suggesting a possible EGFR-associated mechanism of action. Furthermore, DAPI-stained confocal microscopy revealed nuclear morphological changes, including chromatin condensation, nuclear fragmentation, and membrane blebbing, consistent with apoptosis-associated features. Molecular docking studies against wild-type (1M17) and mutant EGFR (4ZAU) showed favorable binding interactions with key active-site residues. Molecular dynamics simulations further confirmed the stability of the PBc1–protein complexes throughout the simulation period. In silico ADMET studies predicted favorable pharmacokinetic and toxicity profiles for the synthesized derivatives. Overall, the integrated experimental and computational findings suggest that PBc1 is a promising compound for further biological and mechanistic investigation.

Graphical abstract