Molecular docking and investigation of 4-(benzylideneamino)- and 4-(benzylamino)-benzenesulfonamide derivatives as potent AChE inhibitors

  • Mesut IşıkEmail author
  • Yeliz Demir
  • Mustafa Durgun
  • Cüneyt Türkeş
  • Adem Necip
  • Şükrü Beydemir
Original Paper


The discovery of acetylcholinesterase inhibitors is important for the treatment of Alzheimer’s disease (AD), known as the most common type of dementia. Due to the side effects of commonly used acetylcholinesterase inhibitors, studies for the detection of new inhibitors are increasing day by day. In this study, we investigated the effects of some sulfonamide derivatives (S1–S4 and S1i–S4i) on AChE enzymes. The best pose of the active compounds to understand the mechanism of possible inhibition in interaction of enzyme-sulfonamide derivative were performed docking studies after in vitro experimental results. ADME-related physicochemical and pharmacokinetic properties of the synthesized 4-aminobenzenesulfonamide derivatives were the compatibility with Lipinski’s rule of five. We found that the synthesized derivatives of sulfonamides show potential inhibitor properties for AChE with Ki constants in the range of 2.54 ± 0.22–299.60 ± 8.73 µM. The derivatives of sulfonamides exhibited different inhibition type. We determined that the derivatives (S1, S1i, S3, and S3i) showed a competitive inhibition effect, whereas others (S2, S2i, S4, and S4i) showed mixed-type inhibition. As a result, the sulfonamide derivatives can be used as an alternative acetylcholinesterase inhibitor due to this effect. Inhibitors with fewer side effects, are thought to be important in the treatment of AD.


Sulfonamide derivatives Alzheimer AChE inhibitor Molecular docking Pharmacokinetic properties 



The authors are grateful for the financial support provided by the Research Foundation of Harran University (Project no. 16180).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11696_2019_988_MOESM1_ESM.docx (93 kb)
Supplementary material 1 (DOCX 93 kb)


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Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2019

Authors and Affiliations

  1. 1.Department of Pharmacy Services, Vocational School of Health ServicesHarran UniversityŞanlıurfaTurkey
  2. 2.Department of Pharmacy Services, Nihat Delibalta Göle Vocational High SchoolArdahan UniversityArdahanTurkey
  3. 3.Department of Chemistry, Faculty of Arts and SciencesHarran UniversityŞanlıurfaTurkey
  4. 4.Department of Biochemistry, Faculty of PharmacyErzincan Binali Yıldırım UniversityErzincanTurkey
  5. 5.Department of Biochemistry, Faculty of PharmacyAnadolu UniversityEskisehirTurkey

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