| Title : New indole derivatives as multitarget anti-Alzheimer's agents: synthesis, biological evaluation and molecular dynamics - Azmy_2023_Future.Med.Chem_15_473 |
| Author(s) : Azmy EM , Nassar IF , Hagras M , Fawzy IM , Hegazy M , Mokhtar MM , Yehia AM , Ismail NS , Lashin WH |
| Ref : Future Med Chem , 15 :473 , 2023 |
|
Abstract :
Background: Alzheimer's disease is a neurological disorder that causes brain cells to shrink and die. Aim: Thirteen novel 'oxathiolanyl', 'pyrazolyl' and 'pyrimidinyl' indole derivatives were designed and synthesized as anti-Alzheimer's disease treatment. Method: In vitro enzyme assay was performed against both AChE and BChE enzymes. In addition, antioxidant assay and cytotoxicity on a normal cell line were determined. Molecular docking and dynamic simulations were conducted to confirm the binding mode in both esterases' active sites. In silico absorption, distribution, metabolism, excretion and toxicity studies were also carried out. Results & conclusion: Compounds 5, 7 and 11 exhibited superior inhibitory activity against acetylcholinesterase and butyrylcholinesterase, with IC(50) values of 0.042 and 3.003 microM, 2.54 and 0.207 microM and 0.052 and 2.529 microM, respectively, compared with donepezil. |
| PubMedSearch : Azmy_2023_Future.Med.Chem_15_473 |
| PubMedID: 37125532 |
Azmy EM, Nassar IF, Hagras M, Fawzy IM, Hegazy M, Mokhtar MM, Yehia AM, Ismail NS, Lashin WH (2023)
New indole derivatives as multitarget anti-Alzheimer's agents: synthesis, biological evaluation and molecular dynamics
Future Med Chem
15 :473
Azmy EM, Nassar IF, Hagras M, Fawzy IM, Hegazy M, Mokhtar MM, Yehia AM, Ismail NS, Lashin WH (2023)
Future Med Chem
15 :473