Skip to content
Research Article Open access CC BY 4.0

Synthesis and Biological Evaluation of Salicylaldehyde-Derived Secondary Amines: Antioxidant, Anti-Inflammatory, and Insecticidal Activities with DFT Insights

Chamseddine Derabli, Noureddine Rahim, Roumaissa Djaba, Sarra Aouidi, Chawki Bensouici, Stephanie Hesse, Houssem Boulebd

Organics · pp. 11–11 · Published 3 Mar 2025

10.3390/org6010011

Abstract

Six secondary amine derivatives derived from salicylaldehyde (SA) were successfully synthesized in good to excellent yields and evaluated for their biological activities. The synthesized compounds exhibited remarkable antioxidant properties, as determined by ABTS and phenanthroline assays. Notably, compound 2 demonstrated an IC50 value of 5.14 ± 0.11 µM in the ABTS assay, approximately six to nine times lower than the standards BHT and BHA. In the phenanthroline assay, all compounds showed inhibition capacities five to ten times greater than BHT and comparable to BHA, with A0.5 values ranging from 9.42 to 31.73 µM. Among these, compound 5 displayed the lowest A0.5 value of 9.42 ± 1.02 µM. The anti-inflammatory activity, assessed through BSA denaturation, revealed that compounds 2 and 5 were the most promising, although their activity was moderate compared to the standard diclofenac. The insecticidal potential of the compounds was evaluated against the storage insect pest Tribolium castaneum. Among the tested derivatives, compounds 1 and 6 exhibited the highest efficacy, achieving maximum mortality rates of 73.31% and 76.67%, respectively, over a seven-day treatment period. Furthermore, the molecular geometry, electronic properties, and intramolecular interactions of all compounds were investigated using DFT calculations. Thermodynamic analyses of the antioxidant mechanisms suggested that the NH bond is the most likely site for free radical attacks. These findings underscore the significant biological potential of the synthesized salicylaldehyde-derived secondary amines.

Salicylaldehyde Antioxidant Chemistry Combinatorial chemistry Organic chemistry Pharmacology Medicine Stereochemistry

References (40)

  1. 1 Krátký, M., Dzurková, M., Janoušek, J., Konečná, K., Trejtnar, F., Stolaříková, J., and Vinšová, J. (2017). Sulfadiazine Salicylaldehyde-Based Schiff Bases: Synthesis, Antimicrobial Activity and Cytotoxicity. Molecules, 22. [DOI]
  2. 2 Montaser, 2019, Synthesis, characterization and antimicrobial activity of Schiff bases from chitosan and salicylaldehyde/TiO2 nanocomposite membrane [DOI]
  3. 3 Peksel, 2014, New p-Substituted Salicylaldehyde Phenylhydrazone Derivatives: Synthesis, Characterization, and Antioxidant Activities [DOI]
  4. 4 2024, Cu(ii) complexes with a salicylaldehyde derivative and α-diimines as co-ligands: Synthesis, characterization, biological activity. Experimental and theoretical approach [DOI]
  5. 5 Koschier, 2007, Influence of salicylaldehyde and methyl salicylate on post-landing behaviour of Frankliniella occidentalis Pergande [DOI]
  6. 6 Kim, 2011, Chemosensitization of Aflatoxigenic Fungi to Antimycin A and Strobilurin Using Salicylaldehyde, a Volatile Natural Compound Targeting Cellular Antioxidation System [DOI]
  7. 7 He, 2023, Discovery of novel salicylaldehyde derivatives incorporating an α-methylene-γ-butyrolactone moiety as fungicidal agents [DOI]
  8. 8 Pelttari, 2007, Antimicrobial Properties of Substituted Salicylaldehydes and Related Compounds [DOI]
  9. 9 Wang, 2017, Natural α-methylenelactam analogues: Design, synthesis and evaluation of α-alkenyl-γ and δ-lactams as potential antifungal agents against Colletotrichum orbiculare [DOI]
  10. 10 Resende, 2020, Recent advances in the synthesis of xanthones and azaxanthones [DOI]
  11. 11 Kirilmis, 2008, Synthesis and antimicrobial activity of some novel derivatives of benzofuran: Part 2. The synthesis and antimicrobial activity of some novel 1-(1-benzofuran-2-yl)-2-mesitylethanone derivatives [DOI]
  12. 12 Rostagno, 2017, Sustainable polyvinyl acetals from bioaromatic aldehydes [DOI]
  13. 13 Huang, 2016, Salicylaldehyde-functionalized block copolymer nano-objects: One-pot synthesis via polymerization-induced self-assembly and their simultaneous cross-linking and fluorescence modification [DOI]
  14. 14 Wu, 2022, Optical and thermal properties of polymethyl methacrylate (PMMA) bearing phenyl and adamantyl substituents [DOI]
  15. 15 Anju, 2017, Impact of Bis-(3-triethoxysilylpropyl)tetrasulphide on the properties of PMMA/Cellulose composite [DOI]
  16. 16 Wong, 2023, Synthesis of benzylated amine-substituted xanthone derivatives and their antioxidant and anti-inflammatory activities [DOI]
  17. 17 Lambert, 2020, Discovery of novel insecticidal 3-aminopyridyl ureas [DOI]
  18. 18 Djafarou, 2023, Synthesis and evaluation of the antioxidant and anti-tyrosinase activities of thiazolyl hydrazone derivatives and their application in the anti-browning of fresh-cut potato [DOI]
  19. 19 Boulebd, 2020, Substitution effects on the antiradical activity of hydralazine: A DFT analysis [DOI]
  20. 20 Boulebd, 2020, Thermodynamic and Kinetic Studies of the Radical Scavenging Behavior of Hydralazine and Dihydralazine: Theoretical Insights [DOI]
  21. 21 Hamel, D., Rozman, V., and Liška, A. (2020). Storage of Cereals in Warehouses with or without Pesticides. Insects, 11. [DOI]
  22. 22 Duarte, 2024, Stored products insects in Portugal—New data and overview [DOI]
  23. 23 Re, 1999, Antioxidant activity applying an improved ABTS radical cation decolorization assay [DOI]
  24. 24 2021, Einstein–Cartan non-supersymmetric spin-polarised nucleons wall dynamos [DOI]
  25. 25 Kumar, 2013, Evaluation of anti-inflammatory activity of Canthium parviflorum by in-vitro method
  26. 26 Preetha, G., Stanley, J., and Suresh, S. (2023). Toxicity of insecticides to wolf spider (Pardosa pseudoannulata) and rice leaf folder (Cnaphalocrocis medinalis): Assessing the risk of insecticides on spiders in the rice ecosystem. Int. J. Pest Manag., 1–10. [DOI]
  27. 27 Abbott, 1925, A Method of Computing the Effectiveness of an Insecticide [DOI]
  28. 28 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.
  29. 29 Marenich, 2009, 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 [DOI]
  30. 30 Lu, 2012, Multiwfn: A multifunctional wavefunction analyzer [DOI]
  31. 31 Humphrey, 1996, VMD: Visual molecular dynamics [DOI]
  32. 32 Boulebd, 2022, Is cannabidiolic acid an overlooked natural antioxidant? Insights from quantum chemistry calculations [DOI]
  33. 33 Boulebd, 2022, Assessment of the free radical scavenging potential of cannabidiol under physiological conditions: Theoretical and experimental investigations [DOI]
  34. 34 Iskander, 1985, Synthesis of 3,4-dihydro-3-(p-methylphenyl)-1,3,2H-benzoxazine: An undergraduate organic chemistry experiment [DOI]
  35. 35 Tang, 2011, Synthesis of 2,3-diaryl-3,4-dihydro-2H-1,3-benzoxazines and their fungicidal activities [DOI]
  36. 36 Waltz, 2011, Synthesis and Structure—Activity Relationships of a Class of Sodium Iodide Symporter Function Inhibitors [DOI]
  37. 37 Kamble, 2015, Green synthesis and in silico investigation of dihydro-2H-benzo[1,3]oxazine derivatives as inhibitors of Mycobacterium tuberculosis [DOI]
  38. 38 Jung, 2020, Estimating economic damage to cocoa bean production with changes in the spatial distribution of Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) in response to climate change [DOI]
  39. 39 Wakil, W., Kavallieratos, N.G., Usman, M., Gulzar, S., and El-Shafie, H.A.F. (2021). Detection of Phosphine Resistance in Field Populations of Four Key Stored-Grain Insect Pests in Pakistan. Insects, 12. [DOI]
  40. 40 Boulebd, 2020, Comparative study of the radical scavenging behavior of ascorbic acid, BHT, BHA and Trolox: Experimental and theoretical study [DOI]

Cited by 8

Vibrational and electronic signatures of bromo-substituted Schiff bases: Thermal stability and molecular docking studies

Abdulrahman Salim Alharbi, Ebraheem Abdu Musad Saleh, Amal Abdullah Aboras · Journal of Molecular Structure · 2025

Showing 4 of 8 known citations — external sources report more than can currently be individually listed.

Article metrics

Real usage data collected on this platform.

0

Page views

0

PDF downloads

0

Outbound clicks

8

Citations

Views by country

Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".

No views recorded yet.

Traffic sources

Referring site, by host.

No traffic recorded yet.

Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.