Synthesis, molecular modeling studies, ADME prediction of arachidonic acid carbamate derivatives, and evaluation of their acetylcholinesterase activity

Kalin T. N., KILIÇ D., ARSLAN F., Colak O., ALTUNDAŞ A.

DRUG DEVELOPMENT RESEARCH, cilt.81, sa.2, ss.232-241, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 81 Sayı: 2
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1002/ddr.21621
  • Dergi Adı: DRUG DEVELOPMENT RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.232-241
  • Anahtar Kelimeler: AChE inhibition, anandamide, carbamates, molecular docking, ANANDAMIDE, INHIBITORS, DEMENTIA, ROLES
  • Atatürk Üniversitesi Adresli: Evet

Özet

In this work, a series of novel anandamide units containing carbamate were designed and synthesized. All the derivatives were evaluated in vitro for their inhibitory potential against the electric eel acetylcholinesterase enzyme (AChE) and showed reversible inhibitions. The compounds 7a, 7d, 7e, and 7f are mixed inhibitors of AChE, while the compounds 7b, 7c, and 7g are uncompetitive (K-i in the range 0.93-8.86 mu M). The kinetic studies revealed that compounds 7b, 7c, 7f, and 7g inhibit considerably AChE activity. Molecular docking analyses were made to evaluate the binding type and interactions of the synthesized compounds to the ligand-binding site of hAChE. It was observed that the docking results were in parallel with the in vitro results. The adsorption, distribution, metabolism, and excretion properties were computed for the compounds, and were found within the acceptable range. This study suggests the compounds 7b, 7c, 7f, and 7g identified as novel reversible AChE inhibitors may be useful lead compounds for the treatment of Alzheimer's disease.