Synthesis, antioxidant activity, theoretical calculations, and molecular docking studies of new 2-(2-hydroxyphenyl)-2-((substituted) amino) acetic acid derivatives | ||
| Egyptian Journal of Chemistry | ||
| Articles in Press, Accepted Manuscript, Available Online from 23 November 2025 | ||
| Document Type: Original Article | ||
| DOI: 10.21608/ejchem.2025.405770.12070 | ||
| Authors | ||
| Mohamed ZABAT* 1; Habiba Rechek2; Chawki Bensouici3; Cherif Behloul4 | ||
| 1PhD Candidate—Organic Chemistry, Department of Chemistry University of Mentouri Constantine 1, Constantine 25000, Algeria. Assistant Professor-Class A-Faculty of Science and Technology, Department of Matter Science, Mohamed Cherif | ||
| 2Department of Biology of Organisms, Faculty of Sciences of Nature and Life, University of Batna 2, Mostefa Ben Boulaid, Batna 05078, Algeria. | ||
| 3Centre de Recherche en Biotechnologie, Ali Mandjli Nouvelle Ville UV 03 BP E73, Constantine, Algeria. | ||
| 41 Laboratory of Natural Product from Plants and Organic Synthesis, Department of Chemistry, University of Mentouri Constantine 1, Constantine 25000, Algeria. | ||
| Abstract | ||
| The present paper describes the synthesis of five 2-(2-hydroxyphenyl)-2-((substituent) amino) acetic acid derivatives (A–E), which were characterized by ¹H NMR, ¹³C NMR, and IR. Five methods were used to evaluate the antioxidant effect of the synthesized compounds: reducing power, DPPH, ABTS, phenanthroline, and CUPRAC. Compound B showed the highest antioxidant activity in ABTS, DPPH, and phenanthroline tests. Density functional theory (DFT) calculations were performed at the B3LYP/6-31G(d,p) level and were used to optimize the molecular geometries and to calculate key thermodynamic descriptors (BDE, IP, PDE, PA, and ETE), enabling us to identify the HAT and SPLET as more favorable mechanisms in the gas phase and aqueous medium, respectively. Additionally, HOMO-LUMO-based global reactivity parameters, including energy gap (Eg), chemical potential (μ), chemical hardness (η), softness (S), global electrophilicity (ω), maximum charge transfer index (ΔNmax), and electronegativity (χ), were computed in both vacuum and water. Structural parameters, MEP, and IR spectra were also simulated. The calculated properties and molecular descriptor values showed good agreement with the experimental antioxidant findings, indicating a close correlation between theory and experiment. Molecular docking studies indicated potential cholinesterase inhibitory activity for compounds A-E, with compound C exhibiting the strongest binding affinity to AChE and BChE (-9.4 kcal/mol and -8.6 kcal/mol, respectively), suggesting potential cholinesterase inhibitory activity. Additionally, the compounds met Lipinski's rule of five criteria, rated via the SwissADME server. | ||
| Keywords | ||
| Acetic acid derivatives; Mannich-base reaction; antioxidants; phenol; DFT calculation; and molecular docking | ||
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