نويد دست يافته

Optimizing the synthesis of anti-Alzheimer's drug with 1-(4-chlorophenyl)-9H-pyrido [3, 4-b] indole drug core Introduction: Alzheimer's is one of the most prominent types of dementia and one of the most destructive neurological diseases, worldwide. Despite of the efforts in recent years, this disease is incurable. The pathological cause of this disease is not fully knew and researchers believe that a combination of factors such as reducing the amount of acetylcholine (cholinergic hypothesis), amyloid beta aggregation, etc. are effective in causing it. In the cholinergic hypothesis, acetylcholinesterase inhibitors are among the most important agents in the treatment of AD that help to improve the function of the cholinergic system to some extent. In this study, hybrids of pyridinium salts with a drug nucleus 1-(4-chlorophenyl)-9H-pyrido [3, 4-b] indole (beta-carbulin nucleus), a new drug nucleus, were designed, synthesized, and their inhibitory effects on the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were eva‎luated. Materials & Methods: 10 derivatives of the above hybrid with the general name 1-benzyl-3-((1-(phenyl)-9H-pyrido [3, 4-b] indole-3-carboxamido) methyl) pyridin-1-ium (structure 10) synthesized through six steps. Analysis of all synthesized compounds were performed by 1H-NMR and 13C-NMR spectra and also In vitro eva‎luation of the inhibitory effect of AChE and BChE was performed by Elman method. Results: The synthesized compounds showed high inhibitory effects on the enzyme acetylcholinesterase (AChE). Of these compounds, 10b showed better inhibitory activity than others did. In addition, these compounds showed an excellent effect on inhibiting the enzyme butyrylcholinesterase (BChE), which had better effects than donepezil as a base. Compound 10f exhibited the greatest effect on BChE activity. As a result, these synthesized hybrids can be a very promising inhibitor of the enzyme butyrylcholinesterase in the treatment of Alzheimer's patients in the severe stages of the disease.

دونپزيل , بيماري آلزايمر , استيل‌كولين‌استراز , بوتيريل‌كولين‌استراز

donepezil , Alzheimer’s disease , Acetylcholinesterase , Butyrylcholinesterase

Navid Dast Yafte

Dr. Dekamin