Makale detayı · 2025
Structure–activity optimization of Deferasirox–derived aroyl hydrazones: Synthesis, DFT characterization, and mechanistic insights into selective anticancer activity against colon and breast cancer
- Yıl
- 2025
- Tür
- article
Veri kaynağı ayrımı
- YÖKSİS YÖKSİS makale kaydı
- YÖKSİS dergi adı Bioorganic Chemistry
- Katalog eşleşmesi (ISSN) Bioorganic Chemistry
- OpenAlex OpenAlex zenginleştirmesi (özet, atıf, konular)
Özet
OpenAlex · İngilizce
Dysregulated iron metabolism is increasingly recognized as a hallmark of tumor progression in solid malignancies, including colon and breast cancers. Deferasirox (DFX), an oral Fe(III) chelator, exhibits anticancer activity; however, its structural optimization may enhance potency and selectivity. Here, six novel DFX-based aroyl hydrazone derivatives were synthesized, structurally characterized, and evaluated in vitro. Quantum chemical calculations and two-dimensional NMR confirmed their configurations, while molecular dynamics simulations demonstrated stable protein-ligand interactions. Compound 5e exhibited potent and selective cytotoxicity against triple-negative breast cancer (MDA-MB-231) and metastatic colon cancer (SW620) cells. Mechanistic studies revealed that 5e induces apoptosis and cell cycle arrest in a dose-dependent manner, with reactive oxygen species (ROS) generation playing a central role. Increased oxidative stress triggered autophagy, as evidenced by upregulation of Beclin-1, ATG5, and LC3 conversion. Co-treatment with the ROS scavenger N-acetylcysteine significantly reversed these effects, confirming the ROS-mediated mechanism. These findings highlight compound 5e as a multi-targeted anticancer agent warranting further in vivo and combination therapy investigations.
Konular
Atıflar
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8 atıf
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Yerel katalogda bu makaleye atıf yapan 9 yayın (OpenAlex referans eşleşmesi; tam dünya listesi değildir).
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