Computational screening, synthesis and neuroprotective evaluation of small molecule for the treatment of alzheimer's disease
BACKGROUND: Current treatments for Alzheimer’s disease primarily address symptoms, as no definitive therapeutic targets have been identified. OBJECTIVES: This study aims to conduct a virtual screening of small molecules and synthesize and evaluate one of the most promising candidates for Alzheimer...
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| Format: | Article |
| Language: | English |
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Universidad de Antioquia
2024-12-01
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| Series: | Vitae |
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| Online Access: | https://revistas.udea.edu.co/index.php/vitae/article/view/354271 |
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| author | Nerlis Pajaro-Castro Elkin Torres-Sierra, Edwar Cortes-Gonzalez Margaret Paternina Erwin Camacho Pedro Blanco |
| author_facet | Nerlis Pajaro-Castro Elkin Torres-Sierra, Edwar Cortes-Gonzalez Margaret Paternina Erwin Camacho Pedro Blanco |
| author_sort | Nerlis Pajaro-Castro |
| collection | DOAJ |
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BACKGROUND: Current treatments for Alzheimer’s disease primarily address symptoms, as no definitive therapeutic targets have been identified.
OBJECTIVES: This study aims to conduct a virtual screening of small molecules and synthesize and evaluate one of the most promising candidates for Alzheimer’s therapy.
METHODS: Using AutoDock Vina, compounds with drug-like properties were docked against key proteins implicated in Alzheimer's pathology: β-Secretase, γ-Secretase, Pin1, and Cdk5. The molecule with the highest in silico affinity (PubChem ID: 84378305) was synthesized and evaluated experimentally. Cytotoxicity and neuroprotective effects were assessed using the MTT assay in the presence of the Aβ25-35 peptide.
RESULTS: Four candidate molecules showed strong binding affinity, ranging from -6.8 to -9.1 kcal/mol. The results showed that when SK-N-SH cells were simultaneously treated with Aß25-35 peptide (5 µM) and compound 84378305 (0,1 µM), the molecule exhibited significant neuroprotection (33%) after the 48 h of incubation.
CONCLUSION: Findings indicate that this lead compound exhibits potential neuroprotective activity, highlighting its promise as a candidate for further development in Alzheimer’s disease treatment.
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| format | Article |
| id | doaj-art-1461bbab8cc2427a83deabdffc34ade4 |
| institution | Kabale University |
| issn | 0121-4004 2145-2660 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Universidad de Antioquia |
| record_format | Article |
| series | Vitae |
| spelling | doaj-art-1461bbab8cc2427a83deabdffc34ade42025-01-17T03:51:25ZengUniversidad de AntioquiaVitae0121-40042145-26602024-12-0131310.17533/udea.vitae.v31n3a354271Computational screening, synthesis and neuroprotective evaluation of small molecule for the treatment of alzheimer's diseaseNerlis Pajaro-Castro0Elkin Torres-Sierra, Edwar Cortes-Gonzalez1Margaret Paternina 2Erwin Camacho 3Pedro Blanco4Universidad de SucreNatural Product Research Group, Department of Chemistry, University of Tolima, Ibague, ColombiaBiomedical Research Group. School of Basic Sciences. University of Sucre, Sincelejo, 700003, Sucre, ColombiaBiomedical Research Group. School of Basic Sciences. University of Sucre, Sincelejo, 700003, Sucre, ColombiaUniversity of Sucre BACKGROUND: Current treatments for Alzheimer’s disease primarily address symptoms, as no definitive therapeutic targets have been identified. OBJECTIVES: This study aims to conduct a virtual screening of small molecules and synthesize and evaluate one of the most promising candidates for Alzheimer’s therapy. METHODS: Using AutoDock Vina, compounds with drug-like properties were docked against key proteins implicated in Alzheimer's pathology: β-Secretase, γ-Secretase, Pin1, and Cdk5. The molecule with the highest in silico affinity (PubChem ID: 84378305) was synthesized and evaluated experimentally. Cytotoxicity and neuroprotective effects were assessed using the MTT assay in the presence of the Aβ25-35 peptide. RESULTS: Four candidate molecules showed strong binding affinity, ranging from -6.8 to -9.1 kcal/mol. The results showed that when SK-N-SH cells were simultaneously treated with Aß25-35 peptide (5 µM) and compound 84378305 (0,1 µM), the molecule exhibited significant neuroprotection (33%) after the 48 h of incubation. CONCLUSION: Findings indicate that this lead compound exhibits potential neuroprotective activity, highlighting its promise as a candidate for further development in Alzheimer’s disease treatment. https://revistas.udea.edu.co/index.php/vitae/article/view/354271Alzheimer’s diseaseBeta secretasecyclin-dependent kinase 5drug-likegamma secretaseneurodegenerative |
| spellingShingle | Nerlis Pajaro-Castro Elkin Torres-Sierra, Edwar Cortes-Gonzalez Margaret Paternina Erwin Camacho Pedro Blanco Computational screening, synthesis and neuroprotective evaluation of small molecule for the treatment of alzheimer's disease Vitae Alzheimer’s disease Beta secretase cyclin-dependent kinase 5 drug-like gamma secretase neurodegenerative |
| title | Computational screening, synthesis and neuroprotective evaluation of small molecule for the treatment of alzheimer's disease |
| title_full | Computational screening, synthesis and neuroprotective evaluation of small molecule for the treatment of alzheimer's disease |
| title_fullStr | Computational screening, synthesis and neuroprotective evaluation of small molecule for the treatment of alzheimer's disease |
| title_full_unstemmed | Computational screening, synthesis and neuroprotective evaluation of small molecule for the treatment of alzheimer's disease |
| title_short | Computational screening, synthesis and neuroprotective evaluation of small molecule for the treatment of alzheimer's disease |
| title_sort | computational screening synthesis and neuroprotective evaluation of small molecule for the treatment of alzheimer s disease |
| topic | Alzheimer’s disease Beta secretase cyclin-dependent kinase 5 drug-like gamma secretase neurodegenerative |
| url | https://revistas.udea.edu.co/index.php/vitae/article/view/354271 |
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