Synthesis, anticholinesterase activity, molecular docking, and molecular dynamic simulation studies of 1,3,4-oxadiazole derivatives

Durmaz S., Evren A. E., SAĞLIK B. N., YURTTAŞ L., TAY N. F.

ARCHIV DER PHARMAZIE, cilt.355, sa.11, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 355 Sayı: 11
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/ardp.202200294
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: anticholinesterase activity, molecular docking, molecular dynamics simulation, oxadiazole, pyridine, BIOLOGICAL EVALUATION, ACETYLCHOLINESTERASE INHIBITORS, ANTIINFLAMMATORY ACTIVITY, ALZHEIMERS-DISEASE, BUTYRYLCHOLINESTERASE, PYRIDINE, POTENT, DISCOVERY
  • Anadolu Üniversitesi Adresli: Evet

Özet

Two new series of 1,3,4-oxadiazoles bearing pyridine and thiazole heterocycles (4a-h and 5a-h) were synthesized (2,5-disubstituted-1,3,4-oxadiazoles). The structures of these newly synthesized compounds were confirmed by H-1 nuclear magnetic resonance (NMR), C-13 NMR, high-resolution mass spectrometric and Fourier transform infrared spectroscopic methods. All these compounds were evaluated for their enzyme inhibitory activities against two cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). From the studies, we identified compounds 4a, 4h, 5a, 5d, and 5e as selective AChE inhibitors, with IC50 values ranging from 0.023 to 0.037 mu M. Furthermore, docking studies of these compounds were performed at the active sites of their target enzymes. The molecular docking study showed that 5e possessed an ideal docking pose with interactions inside AChE.