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Journals / Sakarya University Journal of Science / 2026 / Volume: 30 Issue: 4

Novel Hydrazone Derivative with 4-(4-Aminophenoxy)-N-methylpicolinamide Moiety: Spectroscopic, Molecular Dynamics, and Docking Studies for Potential Anticancer Activity

Tolga Acar Yeşil(SINOP UNIVERSITY)0000-0001-5983-8447
Ömer Dilek(ISPARTA UNIVERSITY OF APPLIED SCIENCES)0000-0003-1409-782X
Tahir Tilki(SULEYMAN DEMIREL UNIVERSITY)0000-0002-1040-2375
Pages
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Publication Date
2026-08-29
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Molecular dynamics simulations (100 ns, YASARA) confirmed lig-and–protein complex stability, minimal RMSD fluctuations, and consistent hydro-gen bond occupancy under physiological conditions.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Protein kinases such as RAF1 and VEGFR2 regulate key pathways in cell prolifera-tion, differentiation, and angiogenesis, making them promising cancer targets.
📊
Key Findings & Data:Here, we designed and syn-thesized a novel hydrazone incorporating the 4-(4-aminophenoxy)-N-methylpicolinamide pharmacophore to achieve selective kinase inhibition.
💡
Conclusion & Impact:Molecular dynamics simulations (100 ns, YASARA) confirmed lig-and–protein complex stability, minimal RMSD fluctuations, and consistent hydro-gen bond occupancy under physiological conditions.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Hydrazone · Quantum chemical · MD simulation

Abstract

Protein kinases such as RAF1 and VEGFR2 regulate key pathways in cell prolifera-tion, differentiation, and angiogenesis, making them promising cancer targets. However, kinase inhibitor efficacy is often limited by off-target effects, poor pharmacokinetics, and resistance. Hydrazone derivatives, with structural flexibility and multi-target potential, offer a valuable scaffold. Here, we designed and syn-thesized a novel hydrazone incorporating the 4-(4-aminophenoxy)-N-methylpicolinamide pharmacophore to achieve selective kinase inhibition. The compound was characterized via 1H/13C-NMR, FT-IR, and mass spectrometry, confirming its structure and purity. DFT (B3LYP/6-311++G(d,p)) calculations sup-ported the experimental data, providing optimized geometry and electronic in-sights. Molecular docking against RAF1 (PDB: 4ASD) and VEGFR2 (PDB: 5HI2) indicated strong binding through hydrogen bonds, π–π stacking, and hydrophobic interactions. Molecular dynamics simulations (100 ns, YASARA) confirmed lig-and–protein complex stability, minimal RMSD fluctuations, and consistent hydro-gen bond occupancy under physiological conditions.

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Cite This Article

Yeşil, T. A., Dilek, Ö., Tilki, T. (2026). Novel Hydrazone Derivative with 4-(4-Aminophenoxy)-N-methylpicolinamide Moiety: Spectroscopic, Molecular Dynamics, and Docking Studies for Potential Anticancer Activity. Sakarya University Journal of Science, Volume: 30 Issue: 4. https://doi.org/10.16984/saufenbilder.1843089

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