Synthesis and acetylcholinesterase enzyme inhibitory effects of some novel 4,5-Dihydro-1<i>H</i>-1,2,4-triazol-5-one derivatives; an <i>in vitro</i> and <i>in silico</i> study

Medetalibeyoglu H., Turkan F., Manap S., Bursal E., Beytur M., Aras A., ...More

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, vol.41, no.10, pp.4286-4294, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 41 Issue: 10
  • Publication Date: 2023
  • Doi Number: 10.1080/07391102.2022.2066021
  • Journal Name: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core
  • Page Numbers: pp.4286-4294
  • Karadeniz Technical University Affiliated: No

Abstract

In this study, a series of novel Schiff bases (4a-4h) containing 1,2,4-triazole structure were synthesized through a condensation reaction of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones with 3-(4-methylbenzenesulfonyloxy)-benzaldehyde. The structures of 3-alkyl(aryl)-4-[3-(4-methylsulfonyloxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (4a-h) were determined through a range of spectroscopic techniques (FT-IR, H-1 NMR, C-13 NMR, and elemental analysis). In addition, enzyme inhibitory properties of the newly synthesized Schiff bases were determined against acetylcholinesterase (AChE). Their K-i values were calculated in the range of 0.70 +/- 0.07-8.65 +/- 5.6 mu M. Besides, their IC50 values were calculated in the range of 0.43-3.87 mu M. Finally, in silico molecular docking interactions of the compounds with AChE target enzyme (PDB ID:4EY7) were evaluated using Chimera and AutoDock Vina softwares. The lowest binding energy levels (-12.0 kcal/mol) of the compounds 4e and 4g with AChE target enzyme were verified the best binding affinities and molecular interactions. Communicated by Ramaswamy H. Sarma