Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer Agents
In this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives di...
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MDPI AG
2017-06-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/22/7/1067 |
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| author | Bo Li Ai-Ling Huang Yi-Long Zhang Zeng Li Hai-Wen Ding Cheng Huang Xiao-Ming Meng Jun Li |
| author_facet | Bo Li Ai-Ling Huang Yi-Long Zhang Zeng Li Hai-Wen Ding Cheng Huang Xiao-Ming Meng Jun Li |
| author_sort | Bo Li |
| collection | DOAJ |
| description | In this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (selectivity index values from 68 to 305). The Lineweaver-Burk plot and molecular docking study showed that these compounds targeted both the peripheral anionic site (PAS) and catalytic active site (CAS) of AChE. The derivatives also showed a potent self-induced β-amyloid (Aβ) aggregation inhibition and a peroxyl radical absorbance activity. Moreover, compound 4f significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Cytotoxicity assay showed that the low concentration of the derivatives does not affect the viability of the SH-SY5Y neurons. Thus, these hesperetin derivatives are potential multifunctional agents for further development for the treatment of Alzheimer’s disease. |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T08:26:54Z |
| publishDate | 2017-06-01 |
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| series | Molecules |
| spelling | doaj.art-ecf859fb568e4034af4edc69e553082f2022-12-22T03:40:22ZengMDPI AGMolecules1420-30492017-06-01227106710.3390/molecules22071067molecules22071067Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer AgentsBo Li0Ai-Ling Huang1Yi-Long Zhang2Zeng Li3Hai-Wen Ding4Cheng Huang5Xiao-Ming Meng6Jun Li7Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 230000 Hefei, ChinaAnhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 230000 Hefei, ChinaAnhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 230000 Hefei, ChinaAnhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 230000 Hefei, ChinaAnhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 230000 Hefei, ChinaAnhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 230000 Hefei, ChinaAnhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 230000 Hefei, ChinaAnhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 230000 Hefei, ChinaIn this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (selectivity index values from 68 to 305). The Lineweaver-Burk plot and molecular docking study showed that these compounds targeted both the peripheral anionic site (PAS) and catalytic active site (CAS) of AChE. The derivatives also showed a potent self-induced β-amyloid (Aβ) aggregation inhibition and a peroxyl radical absorbance activity. Moreover, compound 4f significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Cytotoxicity assay showed that the low concentration of the derivatives does not affect the viability of the SH-SY5Y neurons. Thus, these hesperetin derivatives are potential multifunctional agents for further development for the treatment of Alzheimer’s disease.http://www.mdpi.com/1420-3049/22/7/1067hesperetin derivativesacetylcholinesterase (AChE)butyrylcholine esterase (BuChE)β-amyloid (Aβ)multifunctional |
| spellingShingle | Bo Li Ai-Ling Huang Yi-Long Zhang Zeng Li Hai-Wen Ding Cheng Huang Xiao-Ming Meng Jun Li Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer Agents Molecules hesperetin derivatives acetylcholinesterase (AChE) butyrylcholine esterase (BuChE) β-amyloid (Aβ) multifunctional |
| title | Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer Agents |
| title_full | Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer Agents |
| title_fullStr | Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer Agents |
| title_full_unstemmed | Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer Agents |
| title_short | Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer Agents |
| title_sort | design synthesis and evaluation of hesperetin derivatives as potential multifunctional anti alzheimer agents |
| topic | hesperetin derivatives acetylcholinesterase (AChE) butyrylcholine esterase (BuChE) β-amyloid (Aβ) multifunctional |
| url | http://www.mdpi.com/1420-3049/22/7/1067 |
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