Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors
Acetylcholinesterase (AChE) is one of the classical targets in the treatment of Alzheimer’s disease (AD). Inhibition of AChE slows down the hydrolysis of acetycholine and increases choline levels, improving the cognitive function. The achieved success of plant-based natural drugs acting as AChE inhi...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/10/3139 |
| _version_ | 1827667541973008384 |
|---|---|
| author | Mariyana Atanasova Ivan Dimitrov Stefan Ivanov Borislav Georgiev Strahil Berkov Dimitrina Zheleva-Dimitrova Irini Doytchinova |
| author_facet | Mariyana Atanasova Ivan Dimitrov Stefan Ivanov Borislav Georgiev Strahil Berkov Dimitrina Zheleva-Dimitrova Irini Doytchinova |
| author_sort | Mariyana Atanasova |
| collection | DOAJ |
| description | Acetylcholinesterase (AChE) is one of the classical targets in the treatment of Alzheimer’s disease (AD). Inhibition of AChE slows down the hydrolysis of acetycholine and increases choline levels, improving the cognitive function. The achieved success of plant-based natural drugs acting as AChE inhibitors, such as galantamine (GAL) from Galanthus genus and huperzine A from Huperzia serrate (approved drug in China), in the treatment of AD, and the fact that natural compounds (NCs) are considered as safer and less toxic compared to synthetic drugs, led us to screen the available NCs (almost 150,000) in the ZINC12 database for AChE inhibitory activity. The compounds were screened virtually by molecular docking, filtered for suitable ADME properties, and 32 ligands from 23 structural groups were selected. The stability of the complexes was estimated via 1 μs molecular dynamics simulation. Ten compounds formed stable complexes with the enzyme and had a vendor and a reasonable price per mg. They were tested for AChE inhibitory and antioxidant activity. Five compounds showed weak AChE inhibition and three of them exhibited high antioxidant activity. |
| first_indexed | 2024-03-10T03:19:48Z |
| format | Article |
| id | doaj.art-0cf891b18ecc4d3cbe1f9fd6168533d7 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T03:19:48Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-0cf891b18ecc4d3cbe1f9fd6168533d72023-11-23T12:21:37ZengMDPI AGMolecules1420-30492022-05-012710313910.3390/molecules27103139Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase InhibitorsMariyana Atanasova0Ivan Dimitrov1Stefan Ivanov2Borislav Georgiev3Strahil Berkov4Dimitrina Zheleva-Dimitrova5Irini Doytchinova6Chemistry Department, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaChemistry Department, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaChemistry Department, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaInstitute of Biodiversity and Ecosystem Research, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaInstitute of Biodiversity and Ecosystem Research, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaChemistry Department, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaChemistry Department, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaAcetylcholinesterase (AChE) is one of the classical targets in the treatment of Alzheimer’s disease (AD). Inhibition of AChE slows down the hydrolysis of acetycholine and increases choline levels, improving the cognitive function. The achieved success of plant-based natural drugs acting as AChE inhibitors, such as galantamine (GAL) from Galanthus genus and huperzine A from Huperzia serrate (approved drug in China), in the treatment of AD, and the fact that natural compounds (NCs) are considered as safer and less toxic compared to synthetic drugs, led us to screen the available NCs (almost 150,000) in the ZINC12 database for AChE inhibitory activity. The compounds were screened virtually by molecular docking, filtered for suitable ADME properties, and 32 ligands from 23 structural groups were selected. The stability of the complexes was estimated via 1 μs molecular dynamics simulation. Ten compounds formed stable complexes with the enzyme and had a vendor and a reasonable price per mg. They were tested for AChE inhibitory and antioxidant activity. Five compounds showed weak AChE inhibition and three of them exhibited high antioxidant activity.https://www.mdpi.com/1420-3049/27/10/3139acetylcholinesterase (AChE)natural compoundsvirtual screeningmolecular dockingmolecular dynaminsAlzheimer’s disease (AD) |
| spellingShingle | Mariyana Atanasova Ivan Dimitrov Stefan Ivanov Borislav Georgiev Strahil Berkov Dimitrina Zheleva-Dimitrova Irini Doytchinova Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors Molecules acetylcholinesterase (AChE) natural compounds virtual screening molecular docking molecular dynamins Alzheimer’s disease (AD) |
| title | Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors |
| title_full | Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors |
| title_fullStr | Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors |
| title_full_unstemmed | Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors |
| title_short | Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors |
| title_sort | virtual screening and hit selection of natural compounds as acetylcholinesterase inhibitors |
| topic | acetylcholinesterase (AChE) natural compounds virtual screening molecular docking molecular dynamins Alzheimer’s disease (AD) |
| url | https://www.mdpi.com/1420-3049/27/10/3139 |
| work_keys_str_mv | AT mariyanaatanasova virtualscreeningandhitselectionofnaturalcompoundsasacetylcholinesteraseinhibitors AT ivandimitrov virtualscreeningandhitselectionofnaturalcompoundsasacetylcholinesteraseinhibitors AT stefanivanov virtualscreeningandhitselectionofnaturalcompoundsasacetylcholinesteraseinhibitors AT borislavgeorgiev virtualscreeningandhitselectionofnaturalcompoundsasacetylcholinesteraseinhibitors AT strahilberkov virtualscreeningandhitselectionofnaturalcompoundsasacetylcholinesteraseinhibitors AT dimitrinazhelevadimitrova virtualscreeningandhitselectionofnaturalcompoundsasacetylcholinesteraseinhibitors AT irinidoytchinova virtualscreeningandhitselectionofnaturalcompoundsasacetylcholinesteraseinhibitors |