{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:02:26Z","timestamp":1790258546900,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>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\u2013I6 and amines A1\u2013A6, 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 \u00b1 0.97 \u00b5M; ABTS IC50 = 11.69 \u00b1 0.43 \u00b5M) lower than BHT (DPPH IC50 = 85.85 \u00b1 3.69 \u00b5M) and BHA (DPPH IC50 = 59.39 \u00b1 1.9 \u00b5M) 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 \u00d7 105 M\u22121s\u22121) and a 100% branching ratio (G), completely outcompeting the HAT mechanism (k = 2.28 \u00d7 10\u22122 M\u22121s\u22121). 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 \u00b1 2.23 \u00b5M) with lower toxicity toward non-tumor cells (Vero IC50 &gt; 400 \u00b5M). Molecular docking studies were conducted to elucidate the binding modes of the active derivatives within the active sites of EGFR, Tubulin, and Topoisomerase II\u03b2, while subsequent 100 ns molecular dynamics simulations validated the structural stability and sustained interaction energies of these predicted complexes.<\/jats:p>","DOI":"10.3390\/ma19183980","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:23:17Z","timestamp":1790011397000},"page":"3980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Experimental and Computational Investigation of Salicylaldehyde-Derived Imine\/Amine Derivatives as Antioxidant and Cytotoxic Agents"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1289-9551","authenticated-orcid":false,"given":"Rania","family":"Boukerzaza","sequence":"first","affiliation":[{"name":"Biotechnologies Laboratory, Higher National School of Biotechnology Taoufik Khaznadar, Nouveau P\u00f4le Universitaire Ali Mendjeli, Constantine 25100, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Chamseddine","family":"Derabli","sequence":"additional","affiliation":[{"name":"Biotechnologies Laboratory, Higher National School of Biotechnology Taoufik Khaznadar, Nouveau P\u00f4le Universitaire Ali Mendjeli, Constantine 25100, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Imene Amine","family":"Khodja","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis of Molecules with Biological Interest, Fr\u00e8res Mentouri Constantine 1 University, Constantine 25017, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5791-3279","authenticated-orcid":false,"given":"Abdellatif","family":"Ben Kaida","sequence":"additional","affiliation":[{"name":"Biotechnologies Laboratory, Higher National School of Biotechnology Taoufik Khaznadar, Nouveau P\u00f4le Universitaire Ali Mendjeli, Constantine 25100, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4876-9429","authenticated-orcid":false,"given":"Jose F.","family":"Costa-Rubio","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Universidad Cat\u00f3lica de Murcia (UCAM), 30107 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Chawki","family":"Bensouici","sequence":"additional","affiliation":[{"name":"Biotechnology Research Center, Constantine 25000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7488-5671","authenticated-orcid":false,"given":"Stephanie","family":"Hesse","sequence":"additional","affiliation":[{"name":"LCP-A2MC, Universit\u00e9 de Lorraine, 5700 Metz, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4468-7898","authenticated-orcid":false,"given":"Horacio","family":"P\u00e9rez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Universidad Cat\u00f3lica de Murcia (UCAM), 30107 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7727-8583","authenticated-orcid":false,"given":"Houssem","family":"Boulebd","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis of Molecules with Biological Interest, Fr\u00e8res Mentouri Constantine 1 University, Constantine 25017, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00204-023-03562-9","article-title":"Reactive oxygen species, toxicity, oxidative stress, and antioxidants: Chronic diseases and aging","volume":"97","author":"Jomova","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chaudhary, P., Janmeda, P., Docea, A.O., Yeskaliyeva, B., Abdull Razis, A.F., Modu, B., Calina, D., and Sharifi-Rad, J. (2023). Oxidative stress, free radicals and antioxidants: Potential crosstalk in the pathophysiology of human diseases. Front. Chem., 11.","DOI":"10.3389\/fchem.2023.1158198"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5594386","DOI":"10.1155\/2024\/5594386","article-title":"A comprehensive review of free radicals, oxidative stress, and antioxidants: Overview, clinical applications, global perspectives, future directions, and mechanisms of antioxidant activity of flavonoid compounds","volume":"2024","author":"Tumilaar","year":"2024","journal-title":"J. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"114606","DOI":"10.1016\/j.biopha.2023.114606","article-title":"Cellular Red-Ox system in health and disease: The latest update","volume":"162","author":"Jena","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41420-024-02278-8","article-title":"Free radicals and their impact on health and antioxidant defenses: A review","volume":"11","author":"Chandimali","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"135083","DOI":"10.1016\/j.molstruc.2023.135083","article-title":"Antioxidant activity of new synthesized imine and its corresponding \u03b1-aminophosphonic acid: Experimental and theoretical evaluation","volume":"1281","author":"Kitouni","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"125","DOI":"10.37349\/eff.2024.00030","article-title":"Recent advances in nano-related natural antioxidants, their extraction methods and applications in the food industry","volume":"2","author":"Kashtiban","year":"2024","journal-title":"Explor. Foods Foodomics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2174\/0113895575363243241129100845","article-title":"Exploring the Versatility of Azine Derivatives: A Comprehensive Review on Synthesis and Biological Applications","volume":"25","author":"Alasmari","year":"2025","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Barras, B.J., Ling, T., and Rivas, F. (2024). Recent advances in chemistry and antioxidant\/anticancer biology of monoterpene and meroterpenoid natural product. Molecules, 29.","DOI":"10.3390\/molecules29010279"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"135789","DOI":"10.1016\/j.molstruc.2023.135789","article-title":"Synthesis, characterization, antibacterial and anticancer activities of some heterocyclic imine compounds","volume":"1289","author":"Bsharat","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2174\/1570180813666161026153743","article-title":"Design, synthesis, antioxidant and anticancer activity of new coumarin derivatives linked with thiazole, isoxazole or pyrazole moiety","volume":"14","author":"Abdellatif","year":"2017","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/aoc.3506","article-title":"Synthesis and antioxidant activities of Schiff bases and their complexes: A review","volume":"30","author":"Kaseem","year":"2016","journal-title":"Appl. Organomet. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"138159","DOI":"10.1016\/j.molstruc.2024.138159","article-title":"Indolyl imine compounds as multi-target agents; synthesis, antidiabetic, anticholinesterase, antioxidant activities and molecular modeling","volume":"1309","author":"Ceyhan","year":"2024","journal-title":"J. Mol. Struct."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"123726","DOI":"10.1016\/j.jorganchem.2025.123726","article-title":"Cycloruthenated thiophene-imines: Novel anticancer agents","volume":"1038","author":"Kiskin","year":"2025","journal-title":"J. Organomet. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Khoshbakht, A., Shiran, J.A., Miran, M., and Sepehri, S. (2024). Synthesis and evaluation of in vitro antioxidant, anticancer, and antibacterial properties of new benzylideneiminophenylthiazole analogues. BMC Chem., 18.","DOI":"10.1186\/s13065-024-01273-5"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Derabli, C., Rahim, N., Djaba, R., Aouidi, S., Bensouici, C., Hesse, S., and Boulebd, H. (2025). Synthesis and Biological Evaluation of Salicylaldehyde-Derived Secondary Amines: Antioxidant, Anti-Inflammatory, and Insecticidal Activities with DFT Insights. Organics, 6.","DOI":"10.3390\/org6010011"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","article-title":"Antioxidant activity applying an improved ABTS radical cation decolorization assay","volume":"26","author":"Re","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/1811199a0","article-title":"Antioxidant determinations by the use of a stable free radical","volume":"181","author":"Blois","year":"1958","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"307","DOI":"10.5264\/eiyogakuzashi.44.307","article-title":"Studies on Products of Browning Reaction. Antioxidative Activities of Products of Browning Reaction Prepared from Glucosamine","volume":"44","author":"Oyaizu","year":"1986","journal-title":"Jpn. J. Nutr. Diet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.talanta.2008.04.055","article-title":"Determination of antioxidant capacities of vegetable oils by ferric-ion spectrophotometric methods","volume":"76","author":"Dianoczki","year":"2008","journal-title":"Talanta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7970","DOI":"10.1021\/jf048741x","article-title":"Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method","volume":"52","author":"Apak","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40824-015-0028-0","article-title":"Mycoplasma detection and elimination are necessary for the application of stem cell from human dental apical papilla to tissue engineering and regenerative medicine","volume":"19","author":"Kim","year":"2015","journal-title":"Biomater. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1055\/s-2002-32073","article-title":"Interference of plant extracts, phytoestrogens and antioxidants with the MTT tetrazolium assay","volume":"68","author":"Bruggisser","year":"2002","journal-title":"Planta Medica"},{"key":"ref_24","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., and Petersson, G.A. (2009). Gaussian 09, Gaussian, Inc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00214-007-0310-x","article-title":"The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: Two new functionals and systematic testing of four M06-class functionals and 12 other functionals","volume":"120","author":"Zhao","year":"2008","journal-title":"Theor. Chem. Acc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1002\/jcc.23715","article-title":"Kinetics of radical-molecule reactions in aqueous solution: A benchmark study of the performance of density functional methods","volume":"35","author":"Galano","year":"2014","journal-title":"J. Comput. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1021\/jp7109127","article-title":"How Well Can New-Generation Density Functionals Describe the Energetics of Bond-Dissociation Reactions Producing Radicals?","volume":"112","author":"Zhao","year":"2008","journal-title":"J. Phys. Chem. A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6378","DOI":"10.1021\/jp810292n","article-title":"Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions","volume":"113","author":"Marenich","year":"2009","journal-title":"J. Phys. Chem. B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jcc.22885","article-title":"Multiwfn: A multifunctional wavefunction analyzer","volume":"33","author":"Lu","year":"2012","journal-title":"J. Comput. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_31","unstructured":"D. E. Shaw Research (2021). Schr\u00f6dinger Release 2022-1: Desmond Molecular Dynamics System, Schr\u00f6dinger. Maestro-Desmond InteroperabilityTools."},{"key":"ref_32","unstructured":"(2025). Schr\u00f6dinger Release 2026-3: Protein Preparation Workflow, Schr\u00f6dinger."},{"key":"ref_33","unstructured":"(2021). Schr\u00f6dinger Release 2021-4: LigPrep, Schr\u00f6dinger. Maestro-Desmond Interoperability Tools."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sousa da Silva, A.W., and Vranken, W.F. (2012). ACPYPE\u2014AnteChamber PYthon Parser interfacE. BMC Res. Notes, 5.","DOI":"10.1186\/1756-0500-5-367"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100241","DOI":"10.1016\/j.softx.2019.100241","article-title":"ACPYPE update for nonuniform 1\u20134 scale factors: Conversion of the GLYCAM06 force field from AMBER to GROMACS","volume":"10","author":"Bernardi","year":"2019","journal-title":"SoftwareX"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H","article-title":"LINCS: A linear constraint solver for molecular simulations","volume":"18","author":"Hess","year":"1997","journal-title":"J. Comput. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/prot.21123","article-title":"Comparison of multiple Amber force fields and development of improved protein backbone parameters","volume":"65","author":"Hornak","year":"2006","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nmeth.3658","article-title":"Parmbsc1: A refined force field for DNA simulations","volume":"13","author":"Ivani","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10465","DOI":"10.1080\/07391102.2024.2349527","article-title":"Enhancing MD simulations: ASGARD\u2019s automated analysis for GROMACS","volume":"43","author":"Nelen","year":"2025","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"g_mmpbsa\u2014A GROMACS Tool for High-Throughput MM-PBSA Calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"109193","DOI":"10.1016\/j.inoche.2022.109193","article-title":"Synthesis, theoretical study, molecular docking and biological activity of nano tridentate (E)-2-((3-hydoxyphenyl)methyl)phenol metal complexes","volume":"137","author":"Diab","year":"2022","journal-title":"Inorg. Chem. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6866","DOI":"10.1021\/acs.macromol.0c00947","article-title":"Implementation of meta-Positioning in Tetrafunctional Benzoxazines: Synthesis, Properties, and Differences in the Polymerized Structure","volume":"53","author":"Minami","year":"2020","journal-title":"Macromolecules"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1021\/acs.macromol.7b00487","article-title":"Synthesis and Thermal Properties of Difunctional Benzoxazines with Attached Oxazine Ring at the Para-, Meta-, and Ortho-Position","volume":"50","author":"Kolanadiyil","year":"2017","journal-title":"Macromolecules"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1080\/03602559.2015.1098680","article-title":"Synthesis and Spectral Characterization of Cross Linked Rigid Structured Schiff Base Polymers: Effect of Substituent Position Changes on Optical, Electrical, and Thermal Properties","volume":"55","author":"Dineshkumar","year":"2016","journal-title":"Polym.-Plast. Technol. Eng."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"17492","DOI":"10.1039\/D4NJ02683G","article-title":"Discovery of Schiff bases as potent antibacterial and antifungal agents","volume":"48","year":"2024","journal-title":"New J. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Rafique, B., Kalsoom, S., Sajini, A.A., Ismail, H., and Iqbal, M. (2022). Synthesis, Characterization, Biological Evaluation and DNA Interaction Studies of 4-Aminophenol Derivatives: Theoretical and Experimental Approach. Molecules, 27.","DOI":"10.3390\/molecules27041352"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bader, R.F.W. (1990). Atoms in Molecules: A Quantum Theory, Oxford University Press.","DOI":"10.1093\/oso\/9780198551683.001.0001"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"112528","DOI":"10.1016\/j.phytochem.2020.112528","article-title":"Antioxidant action of deprotonated flavonoids: Thermodynamics of sequential proton-loss electron-transfer","volume":"180","author":"Biela","year":"2020","journal-title":"Phytochemistry"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Boulebd, H. (2025). Hydroperoxyl Radical Scavenging Activity of Bromophenols from Marine Red Alga Polysiphonia urceolata: Mechanistic Insights, Kinetic Analysis, and Influence of Physiological Media. Molecules, 30.","DOI":"10.3390\/molecules30081697"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1021\/acs.jcim.6b00310","article-title":"Empirically Fitted Parameters for Calculating pKa Values with Small Deviations from Experiments Using a Simple Computational Strategy","volume":"56","author":"Galano","year":"2016","journal-title":"J. Chem. Inf. Model."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"138044","DOI":"10.1016\/j.ijbiomac.2024.138044","article-title":"A comprehensive DFT-based study of the antioxidant properties of monolignols: Mechanism, kinetics, and influence of physiological environments","volume":"284","author":"Boulebd","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8168","DOI":"10.1021\/acs.joc.4c00851","article-title":"Mechanistic Insights into the Antioxidant and Pro-oxidant Activities of Bromophenols from Marine Algae: A DFT Investigation","volume":"89","author":"Boulebd","year":"2024","journal-title":"J. Org. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.1021\/ja00478a009","article-title":"Symmetry numbers, not statistical factors, should be used in absolute rate theory and in Broensted relations","volume":"100","author":"Pollak","year":"1978","journal-title":"J. Am. Chem. Soc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s00214-007-0328-0","article-title":"Symmetry numbers and chemical reaction rates","volume":"118","author":"Ellingson","year":"2007","journal-title":"Theor. Chem. Acc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1103\/PhysRev.35.1303","article-title":"The penetration of a potential barrier by electrons","volume":"35","author":"Eckart","year":"1930","journal-title":"Phys. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/kin.21540","article-title":"Radical scavenging behavior of butylated hydroxytoluene against oxygenated free radicals in physiological environments: Insights from DFT calculations","volume":"54","author":"Boulebd","year":"2022","journal-title":"Int. J. Chem. Kinet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.1039\/c3cp43319f","article-title":"A physicochemical examination of the free radical scavenging activity of Trolox: Mechanism, kinetics and influence of the environment","volume":"15","author":"Alberto","year":"2013","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ganot, N., Meker, S., Reytman, L., Tzubery, A., and Tshuva, E.Y. (2013). Anticancer metal complexes: Synthesis and cytotoxicity evaluation by the MTT assay. J. Vis. Exp., e50767.","DOI":"10.3791\/50767"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Arunachalam, K., and Sreeja, P.S. (2025). MTT Assay Protocol. Advanced Cell and Molecular Techniques: Protocols for In Vitro and In Vivo Studies, Springer.","DOI":"10.1007\/978-1-0716-4518-5"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/jnci\/53.3.661","article-title":"Breast Tumor Cell Lines From Pleural Effusions","volume":"53","author":"Cailleau","year":"1974","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1016\/j.csbj.2025.06.033","article-title":"Intraline genomic heterogeneity of the triple-negative breast cancer MDA-MB-231-luc-GFP cell line","volume":"27","author":"Pasantes","year":"2025","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_63","unstructured":"Conn, P.M. (2017). Chapter 35\u2014Modeling Breast Cancer in Animals\u2014Considerations for Prevention and Treatment Studies. Animal Models for the Study of Human Disease, Academic Press. [2nd ed.]."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"35733","DOI":"10.1038\/s41598-025-21326-6","article-title":"In-vitro and in-silico study to assess anti breast cancer potential of N-tosyl-indole based hydrazones","volume":"15","author":"Ghaffar","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.55730\/1300-0527.3594","article-title":"Synthesis of new imine-\/amine-bearing imidazo[1,2-a]pyrimidine derivatives and screening of their cytotoxic activity","volume":"47","author":"Atalay","year":"2023","journal-title":"Turk. J. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"108106","DOI":"10.1016\/j.bioorg.2024.108106","article-title":"Exploring 1,2,3-triazole-Schiff\u2019s base hybrids as innovative EGFR inhibitors for the treatment of breast cancer: In vitro and in silico study","volume":"155","author":"Nawareg","year":"2025","journal-title":"Bioorganic Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"135621","DOI":"10.1016\/j.molstruc.2023.135621","article-title":"Design, synthesis and molecular docking of 1,2,4-triazole schiff base hybrids as tubulin, EGFR inhibitors and apoptosis-inducers","volume":"1286","author":"Mohamed","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9213","DOI":"10.1021\/acs.inorgchem.9b00853","article-title":"Synthesis, Structure, Stability, and Inhibition of Tubulin Polymerization by RuII\u2013p-Cymene Complexes of Trimethoxyaniline-Based Schiff Bases","volume":"58","author":"Acharya","year":"2019","journal-title":"Inorg. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e202303070","DOI":"10.1002\/slct.202303070","article-title":"Synthesis, Characterization and Biological Evaluation of New Enamide Fluorinated-Schiff Base Derivatives as Potential Cytotoxic and Apoptosis-Inducing Agents","volume":"8","author":"Toson","year":"2023","journal-title":"ChemistrySelect"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2501377","DOI":"10.1080\/14756366.2025.2501377","article-title":"Synthesis, in vitro and in silico studies of a novel chrysin-ferrocene Schiff base with potent anticancer activity via G1 arrest, caspase-dependent apoptosis and inhibition of topoisomerase II","volume":"40","author":"Break","year":"2025","journal-title":"J. Enzym. Inhib. Med. Chem."}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/19\/18\/3980\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:29:41Z","timestamp":1790256581000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/19\/18\/3980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,19]]},"references-count":70,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ma19183980"],"URL":"https:\/\/doi.org\/10.3390\/ma19183980","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,19]]}}}