Novel acetylcholinesterase inhibitors: Synthesis, docking and inhibitory activity evaluation of 4-benzamido-N-(1-benzylpiperidin-4-yl) benzamide derivatives
The cholinergic hypothesis is one of the basic approaches for designing and discovering novel anti-Alzheimer drugs. Application of the pharmacophore of well-known drugs like donepezil helps us achieve new molecules. In the current project, a new series of benzamide derivatives (6a–6l) were designed...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221171562300512X |
| _version_ | 1797382902131982336 |
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| author | Ahmad Mohammadi-Farani Sara Nazari Mahsa Mohammadi Sahar Jamshidy Navid Amin Hosseini Alireza Aliabadi |
| author_facet | Ahmad Mohammadi-Farani Sara Nazari Mahsa Mohammadi Sahar Jamshidy Navid Amin Hosseini Alireza Aliabadi |
| author_sort | Ahmad Mohammadi-Farani |
| collection | DOAJ |
| description | The cholinergic hypothesis is one of the basic approaches for designing and discovering novel anti-Alzheimer drugs. Application of the pharmacophore of well-known drugs like donepezil helps us achieve new molecules. In the current project, a new series of benzamide derivatives (6a–6l) were designed and synthesized. Spectroscopic techniques (NMR, IR, MS) were utilized for characterization. Subsequently, Ellman’s protocol was carried out for acetylcholinesterase assay and the obtained results were compared to donepezil (IC50 = 0.6 ± 0.05 µM). Compound 6b which bears a chlorine atom at position meta of the phenyl ring was the most potent derivative in this series (IC50 = 0.14 ± 0.03 nM) and exhibited higher activity than donepezil. In addition, molecular docking was performed to explore the binding mode and related interactions. The in silico results demonstrated that compound 6b binds to the active site of the AChE through a hydrogen bond with Trp279. This compound could be suggested as a potential lead compound and more experimental and in vivo tests are needed to prove its eligibility as a drug candidate. |
| first_indexed | 2024-03-08T21:12:13Z |
| format | Article |
| id | doaj.art-40eeb5abe469433097b120133de91869 |
| institution | Directory Open Access Journal |
| issn | 2211-7156 |
| language | English |
| last_indexed | 2024-03-08T21:12:13Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj.art-40eeb5abe469433097b120133de918692023-12-22T05:32:49ZengElsevierResults in Chemistry2211-71562024-01-017101273Novel acetylcholinesterase inhibitors: Synthesis, docking and inhibitory activity evaluation of 4-benzamido-N-(1-benzylpiperidin-4-yl) benzamide derivativesAhmad Mohammadi-Farani0Sara Nazari1Mahsa Mohammadi2Sahar Jamshidy Navid3Amin Hosseini4Alireza Aliabadi5Medical Plant Research Center, Basic Health Sciences Institute, Shahrekord, University of Medical Sciences, Shahrekord, Iran; Department of Physiology and Pharmacology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, IranStudents Research Committee, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; Pharmaceutical Sciences Research Center, Health Institute, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, IranPharmaceutical Sciences Research Center, Health Institute, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, IranPharmaceutical Sciences Research Center, Health Institute, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, IranStudents Research Committee, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; Pharmaceutical Sciences Research Center, Health Institute, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, IranPharmaceutical Sciences Research Center, Health Institute, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; Corresponding author at: Pharmaceutical Sciences Research Center, Health Institute, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.The cholinergic hypothesis is one of the basic approaches for designing and discovering novel anti-Alzheimer drugs. Application of the pharmacophore of well-known drugs like donepezil helps us achieve new molecules. In the current project, a new series of benzamide derivatives (6a–6l) were designed and synthesized. Spectroscopic techniques (NMR, IR, MS) were utilized for characterization. Subsequently, Ellman’s protocol was carried out for acetylcholinesterase assay and the obtained results were compared to donepezil (IC50 = 0.6 ± 0.05 µM). Compound 6b which bears a chlorine atom at position meta of the phenyl ring was the most potent derivative in this series (IC50 = 0.14 ± 0.03 nM) and exhibited higher activity than donepezil. In addition, molecular docking was performed to explore the binding mode and related interactions. The in silico results demonstrated that compound 6b binds to the active site of the AChE through a hydrogen bond with Trp279. This compound could be suggested as a potential lead compound and more experimental and in vivo tests are needed to prove its eligibility as a drug candidate.http://www.sciencedirect.com/science/article/pii/S221171562300512XSynthesisDockingAlzheimerAcetylcholinesteraseDonepezilBenzamide derivatives |
| spellingShingle | Ahmad Mohammadi-Farani Sara Nazari Mahsa Mohammadi Sahar Jamshidy Navid Amin Hosseini Alireza Aliabadi Novel acetylcholinesterase inhibitors: Synthesis, docking and inhibitory activity evaluation of 4-benzamido-N-(1-benzylpiperidin-4-yl) benzamide derivatives Results in Chemistry Synthesis Docking Alzheimer Acetylcholinesterase Donepezil Benzamide derivatives |
| title | Novel acetylcholinesterase inhibitors: Synthesis, docking and inhibitory activity evaluation of 4-benzamido-N-(1-benzylpiperidin-4-yl) benzamide derivatives |
| title_full | Novel acetylcholinesterase inhibitors: Synthesis, docking and inhibitory activity evaluation of 4-benzamido-N-(1-benzylpiperidin-4-yl) benzamide derivatives |
| title_fullStr | Novel acetylcholinesterase inhibitors: Synthesis, docking and inhibitory activity evaluation of 4-benzamido-N-(1-benzylpiperidin-4-yl) benzamide derivatives |
| title_full_unstemmed | Novel acetylcholinesterase inhibitors: Synthesis, docking and inhibitory activity evaluation of 4-benzamido-N-(1-benzylpiperidin-4-yl) benzamide derivatives |
| title_short | Novel acetylcholinesterase inhibitors: Synthesis, docking and inhibitory activity evaluation of 4-benzamido-N-(1-benzylpiperidin-4-yl) benzamide derivatives |
| title_sort | novel acetylcholinesterase inhibitors synthesis docking and inhibitory activity evaluation of 4 benzamido n 1 benzylpiperidin 4 yl benzamide derivatives |
| topic | Synthesis Docking Alzheimer Acetylcholinesterase Donepezil Benzamide derivatives |
| url | http://www.sciencedirect.com/science/article/pii/S221171562300512X |
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