dataset · Zenodo (CERN European Organization for Nuclear Research)
Chemical compounds based on salicylaldehyde derivatives, including six imines and six secondary amines, have been synthesised and evaluated for their antioxidant and anticancer capabilities. In vitro testing across five antioxidant assays showed that imines performed better in electron-transfer tests, while amines demonstrated superior radical scavenging. Among the tested molecules, the amine compound designated A6 displayed the strongest antioxidant performance, outperforming established commercial antioxidants such as BHT and BHA. Theoretical calculations revealed that phenolic hydroxyl groups govern this reactivity through a sequential proton-loss electron-transfer pathway. In cellular evaluations, chlorinated imine derivative I5 demonstrated moderate cytotoxicity against breast cancer cells while maintaining low toxicity toward normal cells. Computational docking and dynamic simulations confirmed that these active compounds form stable interactions with key target proteins, including EGFR, tubulin, and topoisomerase II beta.
Finding molecules that can neutralise damaging free radicals while selectively targeting cancer cells is a central challenge in drug discovery. This research clarifies how subtle chemical modifications, such as converting imines to amines, influence antioxidant mechanisms and cellular toxicity. Identifying compounds that inhibit cancer cells without harming healthy cells provides useful starting points for developing safer therapeutic and protective agents.
This research represents early-stage laboratory discovery. The identified compounds could serve as preliminary chemical leads for pharmaceutical and nutraceutical developers seeking synthetic antioxidants or targeted anticancer agents. However, practical application remains distant, as the molecules have only undergone in vitro cell culture testing and computer simulations, requiring extensive downstream optimisation, formulation, and in vivo safety and efficacy evaluations before clinical or commercial utility can be established.
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Imines, commonly known as Schiff bases, are widely investigated compounds because of their structural versatility and biological properties. In this study, we aimed to evaluate the antioxidant potential of salicylaldehyde-derived imines and to determine how their reduction to the corresponding secondary amines affects their radical-scavenging activity and mechanism of action. Two series of phenolic derivatives, imines I1–I6 and amines A1–A6, were synthesized and assessed using an integrated experimental and theoretical strategy combining five in vitro antioxidant assays with density functional theory calculations. Antioxidant evaluation by DPPH, ABTS, FRAP, phenanthroline, and CUPRAC assays revealed distinct activity profiles for the two series. The imine derivatives were more effective in electron-transfer-based assays, whereas the reduced amines showed stronger DPPH radical-scavenging activity. Compound A6 exhibited the highest overall antioxidant activity, with IC₅₀ values (e.g., DPPH IC₅₀ = 26.7 ± 0.97 µM; ABTS IC₅₀ = 11.69 ± 0.43 µM) lower than BHT (DPPH IC₅₀ = 85.85 ± 3.69 µM) and BHA (DPPH IC₅₀ = 59.39 ± 1.9 µM) in most assays. DFT calculations in aqueous medium indicated that the phenolic OH groups govern antioxidant reactivity and identified SPLET as the dominant mechanism for A6, supported by a remarkably high rate constant (k = 1.40 × 10 5 M⁻¹s⁻¹) and a 100% branching ratio (G), completely outcompeting the HAT mechanism (k = 2.28 × 10 -2 M⁻¹s⁻¹). In addition to the antioxidant investigation, cytotoxicity was assessed in MDA-MB-231 breast cancer cells and Vero normal cells, revealing that the chlorinated derivatives such as I5 combine moderate anticancer activity (MDA-MB-231 IC₅₀ = 122.6 ± 2.23 µM) with lower toxicity toward non-tumor cells (Vero IC₅₀ > 400 µM). Molecular docking studies were conducted to elucidate the binding modes of the active derivatives within the active sites of EGFR, Tubulin, and Topoisomerase IIβ, while subsequent 100 ns molecular dynamics simulations validated the structural stability and sustained interaction energies of these predicted complexes.
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DOI: 10.5281/zenodo.22644646
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