Synthesis, characterization of novel 2-methoxy-6-((3-substituted-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)iminomethyl)phenyl 4-methylbenzoates and their molecular docking parameters with acetylcholinesterase and butyrylcholinesterase: an in silico mechanism and ADMET investigation

Harmankaya A., Beytur M., Manap S., GÜRSOY KOL Ö., Albayrak Ö., Yüksek H.

Journal of the Iranian Chemical Society, cilt.23, sa.2, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 23 Sayı: 2
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1007/s13738-026-03350-z
  • Dergi Adı: Journal of the Iranian Chemical Society
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: ADMET, Characterization, Molecular docking, Schiff base, Synthesis, Triazole
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

In this study, firstly, nine 4-amino-5-substitued-2,4-dihydro-3 H-1,2,4-triazol-3-one compounds (3) registered in the literature, which were required for the study, were synthesized. Then, 2-Formyl-6-methoxyphenyl 4-methylbenzoate (4) was synthesized by the reaction of 2-hydroxy-3-methoxybenzaldehyde with 4-methylbenzoyl chloride in the presence of triethylamine. As a result of the reaction of 3-type compounds with 2-Formyl-6-methoxyphenyl 4-methylbenzoate (4), 9 new 2-methoxy-6-((3-methyl-5-oxo-1,5-dihydro-4 H-1,2,4-triazol-4-yl)iminomethyl)phenyl 4-methylbenzoate (5) compounds were obtained. The structures of the 9 new synthesized compounds were elucidated using IR, 1H-NMR, 13C-NMR and Mass Spectroscopic methods. In addition, molecular docking studies were conducted showing the binding mechanism of Schiff base-derived compounds with Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) enzymes. As a result of molecular docking studies, compounds 5 g and 5i (-8.251) against AChE and compounds 5d and 5e (-10.173) against BChE showed high affinity in protein-ligand complexes. Finally, the absorption, distribution, metabolism, excretion and toxicity parameters (ADMET) of Schiff base derived compounds were investigated by computer-aided program in order to determine possible drug properties.