Journal of Computer-Aided Molecular Design

, Volume 27, Issue 11, pp 951–964 | Cite as

Antioxidant properties of phenolic Schiff bases: structure–activity relationship and mechanism of action

  • El Hassane AnouarEmail author
  • Salwa Raweh
  • Imene Bayach
  • Muhammad Taha
  • Mohd Syukri Baharudin
  • Florent Di Meo
  • Mizaton Hazizul Hasan
  • Aishah Adam
  • Nor Hadiani Ismail
  • Jean-Frédéric F. Weber
  • Patrick TrouillasEmail author


Phenolic Schiff bases are known for their diverse biological activities and ability to scavenge free radicals. To elucidate (1) the structure–antioxidant activity relationship of a series of thirty synthetic derivatives of 2-methoxybezohydrazide phenolic Schiff bases and (2) to determine the major mechanism involved in free radical scavenging, we used density functional theory calculations (B3P86/6-31+(d,p)) within polarizable continuum model. The results showed the importance of the bond dissociation enthalpies (BDEs) related to the first and second (BDEd) hydrogen atom transfer (intrinsic parameters) for rationalizing the antioxidant activity. In addition to the number of OH groups, the presence of a bromine substituent plays an interesting role in modulating the antioxidant activity. Theoretical thermodynamic and kinetic studies demonstrated that the free radical scavenging by these Schiff bases mainly proceeds through proton-coupled electron transfer rather than sequential proton loss electron transfer, the latter mechanism being only feasible at relatively high pH.


Schiff bases Antioxidant DFT Kinetics Free radical scavenging BDE Structure–activity relationship 



The authors thank the “Conseil Régional du Limousin” for CALI (CAlcul en LImousin) and Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi for computing facilities. The authors thank the “Pharmacology and Toxicology Research Laboratory-Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Malaysia” for antioxidant facilities. P.T. gratefully acknowledges the support by the Operational Program Research and Development for Innovations–European Regional Development Fund (project CZ.1.05/2.1.00/03.0058 of the Ministry of Education, Youth and Sports of the Czech Republic). I.B. and P.T. gratefully thank the ‘Association Djerbienne de France’ (ADF) for the financial support.

Supplementary material

10822_2013_9692_MOESM1_ESM.docx (49 kb)
Supplementary material 1 (DOCX 49 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • El Hassane Anouar
    • 1
    Email author
  • Salwa Raweh
    • 1
    • 2
  • Imene Bayach
    • 1
    • 3
  • Muhammad Taha
    • 1
  • Mohd Syukri Baharudin
    • 1
  • Florent Di Meo
    • 4
  • Mizaton Hazizul Hasan
    • 2
  • Aishah Adam
    • 2
  • Nor Hadiani Ismail
    • 1
    • 5
  • Jean-Frédéric F. Weber
    • 1
    • 2
  • Patrick Trouillas
    • 4
    • 6
    • 7
    Email author
  1. 1.Atta-ur-Rahman Institute for Natural Product Discovery (RiND)Universiti Teknologi MARAShah AlamMalaysia
  2. 2.Faculty of PharmacyUniversiti Teknologi MARAShah AlamMalaysia
  3. 3.LCSN-Faculté de PharmacieUniversité de LimogesLimogesFrance
  4. 4.INSERM, UMR-S850/Faculté de PharmacieUniversité de LimogesLimogesFrance
  5. 5.Faculty of Applied SciencesUniversiti Teknologi MARAShah AlamMalaysia
  6. 6.Laboratoire de Chimie des Matériaux NouveauxUniversité de MonsMonsBelgium
  7. 7.Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of SciencePalacký UniversityOlomoucCzech Republic

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