| Title : Novel tetrahydrocarbazole benzyl pyridine hybrids as potent and selective butryl cholinesterase inhibitors with neuroprotective and beta-secretase inhibition activities - Ghobadian_2018_Eur.J.Med.Chem_155_49 |
| Author(s) : Ghobadian R , Mahdavi M , Nadri H , Moradi A , Edraki N , Akbarzadeh T , Sharifzadeh M , Bukhari SNA , Amini M |
| Ref : Eur Journal of Medicinal Chemistry , 155 :49 , 2018 |
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Abstract :
Butyrylcholinesterase (BuChE) inhibitors have become interesting target for treatment of Alzheimer's disease (AD). A series of dual binding site BuChE inhibitors were designed and synthesized based on 2,3,4,9-tetrahydro-1H-carbazole attached benzyl pyridine moieties. In-vitro assay revealed that all of the designed compounds were selective and potent BuChE inhibitors. The most potent BuChE inhibitor was compound 6i (IC50=0.088+/-0.0009muM) with the mixed-type inhibition. Docking study revealed that 6i is a dual binding site BuChE inhibitor. Also, Pharmacokinetic properties for 6i were accurate to Lipinski's rule. In addition, compound 6i demonstrated neuroprotective and beta-secretase (BACE1) inhibition activities. This compound could also inhibit AChE-induced and self-induced Abeta peptide aggregation at concentration of 100muM and 10muM respectively. Generally, the results are presented as new potent selective BuChE inhibitors with a therapeutic potential for the treatment of AD. |
| PubMedSearch : Ghobadian_2018_Eur.J.Med.Chem_155_49 |
| PubMedID: 29857276 |
Ghobadian R, Mahdavi M, Nadri H, Moradi A, Edraki N, Akbarzadeh T, Sharifzadeh M, Bukhari SNA, Amini M (2018)
Novel tetrahydrocarbazole benzyl pyridine hybrids as potent and selective butryl cholinesterase inhibitors with neuroprotective and beta-secretase inhibition activities
Eur Journal of Medicinal Chemistry
155 :49
Ghobadian R, Mahdavi M, Nadri H, Moradi A, Edraki N, Akbarzadeh T, Sharifzadeh M, Bukhari SNA, Amini M (2018)
Eur Journal of Medicinal Chemistry
155 :49