Synthesis, biological evaluation, and bioinformatics analysis of indole analogs on AChE and GST activities

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Cetin A., Türkan F., Toptas M.

MEDICINAL CHEMISTRY RESEARCH, vol.31, no.12, pp.2119-2131, 2022 (SCI-Expanded)

  • Publication Type: Article / Article
  • Volume: 31 Issue: 12
  • Publication Date: 2022
  • Doi Number: 10.1007/s00044-022-02974-z
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED)
  • Page Numbers: pp.2119-2131
  • Van Yüzüncü Yıl University Affiliated: Yes


In this article, we aimed to (1) synthesize novel 3-substitue 2-methyl indole analogs, and (2) evaluate their biological activities against Acetylcholinesterase enzyme (AChE) and Glutathione S-transferase enzyme (GST), (3) predict ADMET and pharmacokinetic properties of the 3-substitue 2-methyl indole analogs (4) reveal the possible interactions between 3-substitue 2-methyl indole analogs and selected enzymes. In vitro enzyme inhibition studies revealed the 3-substitue 2-methyl indole analogs exhibited moderate to good inhibitory activities against AChE and GST enzymes. 2-azido-1-(2-methyl-1H-indol-3-yl)ethanone synthesized was a good inhibitor with the lowest Ki value for both enzymes. Furthermore, a molecular docking study of 3-substitue 2-methyl indole analogs was carried out in the active site of AChE/GST to gain insight into the interaction modes of the synthesized analogs and rationalized structure-activity relationship. The binding energies of the AChE-3-substitue 2-methyl indole analogs’ complexes were found between −9.3 and −6.0 kcal/mol, and the binding energies of the GST-3-substitue 2-methyl indole analogs’ complexes were also found between −11.1 and −7.5 kcal/mol.