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

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Çetin A., Toptas M., Türkan F.

Medicinal Chemistry Research, cilt.31, sa.12, ss.2119-2131, 2022 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 31 Sayı: 12
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1007/s00044-022-02974-z
  • Dergi Adı: Medicinal Chemistry Research
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, Veterinary Science Database
  • Sayfa Sayıları: ss.2119-2131
  • Anahtar Kelimeler: Alzheimer, Docking, Enzyme inhibition, Pharmacokinetic, Spectroscopy, Synthesis
  • Van Yüzüncü Yıl Üniversitesi Adresli: Evet

Özet

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. [Figure not available: see fulltext.]