Novel Uracil-Based Inhibitors of Acetylcholinesterase with Potency for Treating Memory Impairment in an Animal Model of Alzheimer’s Disease
Novel derivatives based on 6-methyluracil and condensed uracil, 2,4-quinazoline-2,4-dione, were synthesized with terminal <i>meta</i>- and <i>para</i>-benzoate moieties in polymethylene chains at the N atoms of the pyrimidine ring. In the synthesized compounds, the polymethyl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/22/7855 |
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| author | Vyacheslav E. Semenov Irina V. Zueva Sofya V. Lushchekina Eduard G. Suleimanov Liliya M. Gubaidullina Marina M. Shulaeva Oksana A. Lenina Konstantin A. Petrov |
| author_facet | Vyacheslav E. Semenov Irina V. Zueva Sofya V. Lushchekina Eduard G. Suleimanov Liliya M. Gubaidullina Marina M. Shulaeva Oksana A. Lenina Konstantin A. Petrov |
| author_sort | Vyacheslav E. Semenov |
| collection | DOAJ |
| description | Novel derivatives based on 6-methyluracil and condensed uracil, 2,4-quinazoline-2,4-dione, were synthesized with terminal <i>meta</i>- and <i>para</i>-benzoate moieties in polymethylene chains at the N atoms of the pyrimidine ring. In the synthesized compounds, the polymethylene chains were varied from having tris- to hexamethylene chains and quaternary ammonium groups; varying substituents (ester, salt, acid) at benzene ring were introduced into the chains and benzoate moieties. In vivo biological experiments demonstrated the potency of these compounds in decreasing the number of β-amyloid plaques and their suitability for the treatment of memory impairment in a transgenic model of Alzheimer’s disease. |
| first_indexed | 2024-03-09T18:06:58Z |
| format | Article |
| id | doaj.art-76c4a99ab68949beb4f66f6db588bdb1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:06:58Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-76c4a99ab68949beb4f66f6db588bdb12023-11-24T09:22:15ZengMDPI AGMolecules1420-30492022-11-012722785510.3390/molecules27227855Novel Uracil-Based Inhibitors of Acetylcholinesterase with Potency for Treating Memory Impairment in an Animal Model of Alzheimer’s DiseaseVyacheslav E. Semenov0Irina V. Zueva1Sofya V. Lushchekina2Eduard G. Suleimanov3Liliya M. Gubaidullina4Marina M. Shulaeva5Oksana A. Lenina6Konstantin A. Petrov7Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, RussiaEmanuel Institute of Biochemical Physics, Kosygina st. 4, Moscow 119334, RussiaAlexander Butlerov Institute of Chemistry, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlyovskaya str. 18, Kazan 420008, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, RussiaNovel derivatives based on 6-methyluracil and condensed uracil, 2,4-quinazoline-2,4-dione, were synthesized with terminal <i>meta</i>- and <i>para</i>-benzoate moieties in polymethylene chains at the N atoms of the pyrimidine ring. In the synthesized compounds, the polymethylene chains were varied from having tris- to hexamethylene chains and quaternary ammonium groups; varying substituents (ester, salt, acid) at benzene ring were introduced into the chains and benzoate moieties. In vivo biological experiments demonstrated the potency of these compounds in decreasing the number of β-amyloid plaques and their suitability for the treatment of memory impairment in a transgenic model of Alzheimer’s disease.https://www.mdpi.com/1420-3049/27/22/7855acetylcholinesterase6-methyluracilinhibitorsperipheral anionic siteAlzheimer’s disease |
| spellingShingle | Vyacheslav E. Semenov Irina V. Zueva Sofya V. Lushchekina Eduard G. Suleimanov Liliya M. Gubaidullina Marina M. Shulaeva Oksana A. Lenina Konstantin A. Petrov Novel Uracil-Based Inhibitors of Acetylcholinesterase with Potency for Treating Memory Impairment in an Animal Model of Alzheimer’s Disease Molecules acetylcholinesterase 6-methyluracil inhibitors peripheral anionic site Alzheimer’s disease |
| title | Novel Uracil-Based Inhibitors of Acetylcholinesterase with Potency for Treating Memory Impairment in an Animal Model of Alzheimer’s Disease |
| title_full | Novel Uracil-Based Inhibitors of Acetylcholinesterase with Potency for Treating Memory Impairment in an Animal Model of Alzheimer’s Disease |
| title_fullStr | Novel Uracil-Based Inhibitors of Acetylcholinesterase with Potency for Treating Memory Impairment in an Animal Model of Alzheimer’s Disease |
| title_full_unstemmed | Novel Uracil-Based Inhibitors of Acetylcholinesterase with Potency for Treating Memory Impairment in an Animal Model of Alzheimer’s Disease |
| title_short | Novel Uracil-Based Inhibitors of Acetylcholinesterase with Potency for Treating Memory Impairment in an Animal Model of Alzheimer’s Disease |
| title_sort | novel uracil based inhibitors of acetylcholinesterase with potency for treating memory impairment in an animal model of alzheimer s disease |
| topic | acetylcholinesterase 6-methyluracil inhibitors peripheral anionic site Alzheimer’s disease |
| url | https://www.mdpi.com/1420-3049/27/22/7855 |
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