We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Novel indolotacrine hybrids as acetylcholinesterase inhibitors: design, synthesis, biological evaluation, and molecular docking studies.
- Authors
Babaee, Saeed; Zolfigol, Mohammad Ali; Chehardoli, Gholamabbas; Faramarzi, Mohammad Ali; Mojtabavi, Somayeh; Akbarzadeh, Tahmineh; Hariri, Roshanak; Rastegari, Arezoo; Homayouni Moghadam, Farshad; Mahdavi, Mohammad; Najafi, Zahra
- Abstract
A new class of indolotacrine hybrids including cyclopenta- and cyclohexa-indolotacrine derivatives was designed, synthesized, and assessed as acetylcholinesterase inhibitors (AChEIs). Some of the designed derivatives indicated a good inhibitory effect against acetylcholinesterase (AChE). Among them, cyclopenta-indolotacrine hybrids showed a slightly better anti-AChE activity than cyclohexa-indolotacrine hybrids. Compound 5-amino-4-(4-chlorophenyl)-2-(1H-indol-3-yl)-4,6,7,8-tetrahydrocyclopenta[b]pyrano[3,2-e]pyridine-3-carbonitrile (8g) including 4-chlorophenyl and cyclopentane ring showed the best AChE inhibitory activity with IC50 value of 0.4 µM. The kinetic study indicated that compound 8g acted as a competitive inhibitor. Based on molecular docking results, it occupied both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE. Using a neuroprotective assay against H2O2-induced cell death in PC12 neurons, only compound 8b with 4-methoxyphenyl moiety and cyclopentane ring illustrated significant protection (P < 0.0001) at a concentration of 100 μM compared to quercetin at a concentration of 10 μM (P < 0.0001). In silico ADME studies estimated good drug-likeness for the designed compounds. As a result, these indolotacrine hybrids can be a very encouraging AChE inhibitor to treat Alzheimer's disease.
- Subjects
ACETYLCHOLINESTERASE inhibitors; TACRINE; MOLECULAR docking; ALZHEIMER'S disease; KINASE inhibitors; ACETYLCHOLINESTERASE; PHOSPHATASE inhibitors; CYCLOPENTANE
- Publication
Journal of the Iranian Chemical Society, 2023, Vol 20, Issue 5, p1049
- ISSN
1735-207X
- Publication type
Article
- DOI
10.1007/s13738-022-02726-1