Synthesis And In-Silico Anti-Cancer Potential of N-Aryl-Keto-Nitrone As A Spin Adducts
Rita S. Adam 1*
Journal of Angiotherapy 8(1) 1-11 https://doi.org/10.25163/angiotherapy.819437
Submitted: 19 December 2023 Revised: 18 January 2024 Published: 21 January 2024
Abstract
Introduction: This study explores N-Aryl-Keto-Nitrone synthesis and its impact on spin-trapping chemistry, revealing crucial insights into free radicals' roles in diseases. While aldo-nitrones are well-studied, keto-nitrones, especially linear ones, are underexplored as spin traps. Seven novel keto-nitrones are introduced, and their efficacy in capturing carbon-centered radicals is assessed. Methods: Synthesis involves dissolving N-aryl-nitroso compounds in THF, adding NaOH, and introducing dimethyl or diethyl bromo malonate. Thin-layer chromatography monitors the reaction, yielding crude keto-nitrones purified through extraction, drying, and recrystallization. Spin trapping experiments use various radical sources, analyzed by EPR at room temperature. In silico predictions assess ADME properties, P-glycoprotein substrate potential, and molecular docking explores binding orientations with VEGFR2 and EGFR. Results: Diverse N-aryl-keto-nitrones with unique structures and reactivity towards carbon-centered radicals are successfully synthesized. Enhanced interpretability is observed in penta-deuterated compounds N6 and N7. The compounds exhibit varying lipophilicity and resistance to oxidative or reducing agents, broadening their potential applications. In silico predictions show favorable properties, and the compounds demonstrate potential as VEGFR1 downregulators, suggesting applications in disrupting angiogenic signals in cancers. Conclusion: This research advances spin-trapping chemistry by introducing linear keto-nitrones as effective agents. The synthesized compounds demonstrate versatility and impact, with ongoing research focusing on additional applications and refinement for practical use.
Keywords: Nitrones, Electron paramagnetic resonance spectroscopy, Spin trap, Free radicals, anti-angiogenesis.
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