Design and synthesis of new indole drug candidates to treat Alzheimer’s disease and targeting neuro-inflammation using a multi-target-directed ligand (MTDL) strategy
A novel series of indole-based compounds was designed, synthesised, and evaluated as anti-Alzheimer’s and anti-neuroinflammatory agents. The designed compounds were in vitro evaluated for their AChE and BuChE inhibitory activities. The obtained results revealed that compound 3c had higher selectivit...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2126464 |
| _version_ | 1798000518289686528 |
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| author | Phoebe F. Lamie Maha M. Abdel-Fattah John N. Philoppes |
| author_facet | Phoebe F. Lamie Maha M. Abdel-Fattah John N. Philoppes |
| author_sort | Phoebe F. Lamie |
| collection | DOAJ |
| description | A novel series of indole-based compounds was designed, synthesised, and evaluated as anti-Alzheimer’s and anti-neuroinflammatory agents. The designed compounds were in vitro evaluated for their AChE and BuChE inhibitory activities. The obtained results revealed that compound 3c had higher selectivity for AChE than BuChE, while, 4a, 4b, and 4d showed selectivity for BuChE over AChE. Compounds 5b, 6b, 7c, and 10b exerted dual AChE/BuChE inhibitory activities at nanomolar range. Compounds 5b and 6b had the ability to inhibit the self-induced Aβ amyloid aggregation. Different anti-inflammatory mediators (NO, COX-2, IL-1β, and TNF-α) were assessed for compounds 5b and 6b. Cytotoxic effect of 5b and 6b against human neuroblastoma (SH-SY5Y) and normal hepatic (THLE2) cell lines was screened in vitro. Molecular docking study inside rhAChE and hBuChE active sites, drug-likeness, and ADMET prediction were performed. |
| first_indexed | 2024-04-11T11:21:33Z |
| format | Article |
| id | doaj.art-4fc73e36c7ed42c7938bd974b96b3387 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-11T11:21:33Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-4fc73e36c7ed42c7938bd974b96b33872022-12-22T04:27:01ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013712660267810.1080/14756366.2022.2126464Design and synthesis of new indole drug candidates to treat Alzheimer’s disease and targeting neuro-inflammation using a multi-target-directed ligand (MTDL) strategyPhoebe F. Lamie0Maha M. Abdel-Fattah1John N. Philoppes2Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptA novel series of indole-based compounds was designed, synthesised, and evaluated as anti-Alzheimer’s and anti-neuroinflammatory agents. The designed compounds were in vitro evaluated for their AChE and BuChE inhibitory activities. The obtained results revealed that compound 3c had higher selectivity for AChE than BuChE, while, 4a, 4b, and 4d showed selectivity for BuChE over AChE. Compounds 5b, 6b, 7c, and 10b exerted dual AChE/BuChE inhibitory activities at nanomolar range. Compounds 5b and 6b had the ability to inhibit the self-induced Aβ amyloid aggregation. Different anti-inflammatory mediators (NO, COX-2, IL-1β, and TNF-α) were assessed for compounds 5b and 6b. Cytotoxic effect of 5b and 6b against human neuroblastoma (SH-SY5Y) and normal hepatic (THLE2) cell lines was screened in vitro. Molecular docking study inside rhAChE and hBuChE active sites, drug-likeness, and ADMET prediction were performed.https://www.tandfonline.com/doi/10.1080/14756366.2022.2126464IndoleAlzheimer’s diseaseinflammationAChEBuChE |
| spellingShingle | Phoebe F. Lamie Maha M. Abdel-Fattah John N. Philoppes Design and synthesis of new indole drug candidates to treat Alzheimer’s disease and targeting neuro-inflammation using a multi-target-directed ligand (MTDL) strategy Journal of Enzyme Inhibition and Medicinal Chemistry Indole Alzheimer’s disease inflammation AChE BuChE |
| title | Design and synthesis of new indole drug candidates to treat Alzheimer’s disease and targeting neuro-inflammation using a multi-target-directed ligand (MTDL) strategy |
| title_full | Design and synthesis of new indole drug candidates to treat Alzheimer’s disease and targeting neuro-inflammation using a multi-target-directed ligand (MTDL) strategy |
| title_fullStr | Design and synthesis of new indole drug candidates to treat Alzheimer’s disease and targeting neuro-inflammation using a multi-target-directed ligand (MTDL) strategy |
| title_full_unstemmed | Design and synthesis of new indole drug candidates to treat Alzheimer’s disease and targeting neuro-inflammation using a multi-target-directed ligand (MTDL) strategy |
| title_short | Design and synthesis of new indole drug candidates to treat Alzheimer’s disease and targeting neuro-inflammation using a multi-target-directed ligand (MTDL) strategy |
| title_sort | design and synthesis of new indole drug candidates to treat alzheimer s disease and targeting neuro inflammation using a multi target directed ligand mtdl strategy |
| topic | Indole Alzheimer’s disease inflammation AChE BuChE |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2126464 |
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