Novel diazen-bis(phenoxy-1,2,3-triazole-N-phenylacetamide) derivatives as potent anti-cholinesterase, anti-α-glycosidase and anti-α-amylase agents: In vitro and in silico evaluations

Kermaninia S., Mohammadi-Khanaposhtani M., Bagherian N., Dastyafteh N., Moradkhani F., Saeedi S., ...Daha Fazla

Journal of Molecular Structure, cilt.1348, 2025 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1348
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.molstruc.2025.143490
  • Dergi Adı: Journal of Molecular Structure
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Anahtar Kelimeler: acetylcholinesterase, butyrylcholinesterase, Diazen, Phenoxy-1,2,3-triazol-acetamide, α-Glycosidase
  • Atatürk Üniversitesi Adresli: Evet

Özet

In this work, new diazen-bis(phenoxy-1,2,3-triazole-N-phenylacetamide) derivatives 9a-n were designed, synthesized, and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors that are two important targets in the treatment of Alzheimer's disease (AD). These compounds were also evaluated against α-amylase and α-glycosidase because they were structurally similar to some inhibitors of these enzymes. In vitro evaluations demonstrated that, with the exception of α-glycosidase, most of the new synthesized compounds showed significant inhibitory effect against the studied enzymes. In this regard, the most potent compound against AChE and BChE (compound 9 h) was around 2 times more potent than standard inhibitor (tacrine) against these enzymes. Moreover, the most potent compound against α-amylase (compound 9i) was around 3.8 folds more potent than standard inhibitor (acarbose). Molecular modeling study demonstrated that these most potent compounds were attached to the active sites of the related target enzymes with the binding energies more favorable than used standard inhibitors. Furthermore, docking studies exhibited that compound 9 h interacted with both the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of the binding sites AChE and BChE. These interactions are valuable to select a compound as the lead compound in the treatment of AD.