Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease
Fifteen chalcone derivatives 3a–3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self‐induced Aβ1‐42 aggregation effectively ranged from 45.9–94.5 % at 20 μM, and acted as potential antioxidants. T...
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| Veröffentlicht in: | Chemistry & biodiversity 2021-11, Vol.18 (11), p.e2100341-n/a |
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| creator | Wang, Xiao‐Qin Zhou, Lu‐Yi Tan, Ren‐Xian Liang, Guo‐Peng Fang, Si‐Xian Li, Wei Xie, Mei Wen, Yu‐Hao Wu, Jia‐Qiang Chen, Yi‐Ping |
| description | Fifteen chalcone derivatives 3a–3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self‐induced Aβ1‐42 aggregation effectively ranged from 45.9–94.5 % at 20 μM, and acted as potential antioxidants. Their structure‐activity relationships were summarized. In particular, (2E)‐3‐[4‐(dimethylamino)phenyl]‐1‐(pyridin‐2‐yl)prop‐2‐en‐1‐one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 μM, and it could disassemble the self‐induced Aβ1‐42 aggregation fibrils with ratio of 57.1 % at 20 μM concentration. In addition, compound 3g displayed good chelating ability for Cu2+, and could effectively inhibit and disaggregate Cu2+‐induced Aβ aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aβ1‐42‐induced SH‐SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine‐induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy. |
| doi_str_mv | 10.1002/cbdv.202100341 |
| format | Article |
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In vitro studies revealed that these compounds inhibited self‐induced Aβ1‐42 aggregation effectively ranged from 45.9–94.5 % at 20 μM, and acted as potential antioxidants. Their structure‐activity relationships were summarized. In particular, (2E)‐3‐[4‐(dimethylamino)phenyl]‐1‐(pyridin‐2‐yl)prop‐2‐en‐1‐one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 μM, and it could disassemble the self‐induced Aβ1‐42 aggregation fibrils with ratio of 57.1 % at 20 μM concentration. In addition, compound 3g displayed good chelating ability for Cu2+, and could effectively inhibit and disaggregate Cu2+‐induced Aβ aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aβ1‐42‐induced SH‐SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine‐induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy.</description><identifier>ISSN: 1612-1872</identifier><identifier>EISSN: 1612-1880</identifier><identifier>DOI: 10.1002/cbdv.202100341</identifier><identifier>PMID: 34510699</identifier><language>eng</language><publisher>Switzerland: Wiley Subscription Services, Inc</publisher><subject>Agglomeration ; Alzheimer Disease - drug therapy ; Alzheimer Disease - metabolism ; Alzheimer's disease ; Amyloid beta-Peptides - antagonists & inhibitors ; Amyloid beta-Peptides - metabolism ; Animals ; Antioxidants ; Aβ aggregation ; Cell Survival - drug effects ; chalcone ; Chalcones - chemical synthesis ; Chalcones - chemistry ; Chalcones - pharmacology ; Chelation ; Copper ; Copper - pharmacology ; Cytotoxicity ; Drug Design ; Fibrils ; Humans ; Memory Disorders - chemically induced ; Memory Disorders - drug therapy ; metal chelating ; Mice ; multifunctional ; Neurodegenerative diseases ; Neuroprotective Agents - chemical synthesis ; Neuroprotective Agents - chemistry ; Neuroprotective Agents - pharmacology ; Peptide Fragments - antagonists & inhibitors ; Peptide Fragments - metabolism ; Protein Aggregates - drug effects ; Scopolamine ; Toxicity ; Tumor Cells, Cultured</subject><ispartof>Chemistry & biodiversity, 2021-11, Vol.18 (11), p.e2100341-n/a</ispartof><rights>2021 Wiley‐VHCA AG, Zurich, Switzerland</rights><rights>2021 Wiley-VHCA AG, Zurich, Switzerland.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3731-23b197ce69512eabae82530ac12154ba1a2ac064155dd2eb50d0f7dcc62c4e543</citedby><cites>FETCH-LOGICAL-c3731-23b197ce69512eabae82530ac12154ba1a2ac064155dd2eb50d0f7dcc62c4e543</cites><orcidid>0000-0003-2563-5048</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcbdv.202100341$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcbdv.202100341$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34510699$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Xiao‐Qin</creatorcontrib><creatorcontrib>Zhou, Lu‐Yi</creatorcontrib><creatorcontrib>Tan, Ren‐Xian</creatorcontrib><creatorcontrib>Liang, Guo‐Peng</creatorcontrib><creatorcontrib>Fang, Si‐Xian</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Xie, Mei</creatorcontrib><creatorcontrib>Wen, Yu‐Hao</creatorcontrib><creatorcontrib>Wu, Jia‐Qiang</creatorcontrib><creatorcontrib>Chen, Yi‐Ping</creatorcontrib><title>Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease</title><title>Chemistry & biodiversity</title><addtitle>Chem Biodivers</addtitle><description>Fifteen chalcone derivatives 3a–3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self‐induced Aβ1‐42 aggregation effectively ranged from 45.9–94.5 % at 20 μM, and acted as potential antioxidants. Their structure‐activity relationships were summarized. In particular, (2E)‐3‐[4‐(dimethylamino)phenyl]‐1‐(pyridin‐2‐yl)prop‐2‐en‐1‐one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 μM, and it could disassemble the self‐induced Aβ1‐42 aggregation fibrils with ratio of 57.1 % at 20 μM concentration. In addition, compound 3g displayed good chelating ability for Cu2+, and could effectively inhibit and disaggregate Cu2+‐induced Aβ aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aβ1‐42‐induced SH‐SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine‐induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy.</description><subject>Agglomeration</subject><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-Peptides - antagonists & inhibitors</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Aβ aggregation</subject><subject>Cell Survival - drug effects</subject><subject>chalcone</subject><subject>Chalcones - chemical synthesis</subject><subject>Chalcones - chemistry</subject><subject>Chalcones - pharmacology</subject><subject>Chelation</subject><subject>Copper</subject><subject>Copper - pharmacology</subject><subject>Cytotoxicity</subject><subject>Drug Design</subject><subject>Fibrils</subject><subject>Humans</subject><subject>Memory Disorders - chemically induced</subject><subject>Memory Disorders - drug therapy</subject><subject>metal chelating</subject><subject>Mice</subject><subject>multifunctional</subject><subject>Neurodegenerative diseases</subject><subject>Neuroprotective Agents - chemical synthesis</subject><subject>Neuroprotective Agents - chemistry</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Peptide Fragments - antagonists & inhibitors</subject><subject>Peptide Fragments - metabolism</subject><subject>Protein Aggregates - drug effects</subject><subject>Scopolamine</subject><subject>Toxicity</subject><subject>Tumor Cells, Cultured</subject><issn>1612-1872</issn><issn>1612-1880</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkbtv2zAQh4mgQeykXTsWBDokQ-yQJ1GP0bXzAhJk6GMVTtTJpkFTrig5cP760HDiAl0y8Xj8-AF3P8a-SjGWQsCVLqvNGASESxTLIzaUiYSRzDLx6VCnMGCn3i8DH_rZCRtEsZIiyfMha2bkzdxd8p9b1y1C7S85uopfb9D22JnG8abm0wVa3TjiM2rNJrQ35Dl6_tjbztS90zsQLZ_MyXXhZY7G-Y5P7MuCzIrac89nxhN6-syOa7SevrydZ-z3zfWv6d3o4en2fjp5GOkojeQIolLmqaYkVxIIS6QMVCRQS5AqLlEioBZJLJWqKqBSiUrUaaV1AjomFUdn7GLvXbfN3558V6yM12QtOmp6X4BKASKRKhXQ7_-hy6ZvwziBSmQGIOJkJxzvKd023rdUF-vWrLDdFlIUuyiKXRTFIYrw4dubti9XVB3w990HIN8Dz8bS9gNdMf0x-_NP_gq_cpVJ</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Wang, Xiao‐Qin</creator><creator>Zhou, Lu‐Yi</creator><creator>Tan, Ren‐Xian</creator><creator>Liang, Guo‐Peng</creator><creator>Fang, Si‐Xian</creator><creator>Li, Wei</creator><creator>Xie, Mei</creator><creator>Wen, Yu‐Hao</creator><creator>Wu, Jia‐Qiang</creator><creator>Chen, Yi‐Ping</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2563-5048</orcidid></search><sort><creationdate>202111</creationdate><title>Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease</title><author>Wang, Xiao‐Qin ; Zhou, Lu‐Yi ; Tan, Ren‐Xian ; Liang, Guo‐Peng ; Fang, Si‐Xian ; Li, Wei ; Xie, Mei ; Wen, Yu‐Hao ; Wu, Jia‐Qiang ; Chen, Yi‐Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3731-23b197ce69512eabae82530ac12154ba1a2ac064155dd2eb50d0f7dcc62c4e543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Agglomeration</topic><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer's disease</topic><topic>Amyloid beta-Peptides - antagonists & inhibitors</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Aβ aggregation</topic><topic>Cell Survival - drug effects</topic><topic>chalcone</topic><topic>Chalcones - chemical synthesis</topic><topic>Chalcones - chemistry</topic><topic>Chalcones - pharmacology</topic><topic>Chelation</topic><topic>Copper</topic><topic>Copper - pharmacology</topic><topic>Cytotoxicity</topic><topic>Drug Design</topic><topic>Fibrils</topic><topic>Humans</topic><topic>Memory Disorders - chemically induced</topic><topic>Memory Disorders - drug therapy</topic><topic>metal chelating</topic><topic>Mice</topic><topic>multifunctional</topic><topic>Neurodegenerative diseases</topic><topic>Neuroprotective Agents - chemical synthesis</topic><topic>Neuroprotective Agents - chemistry</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Peptide Fragments - antagonists & inhibitors</topic><topic>Peptide Fragments - metabolism</topic><topic>Protein Aggregates - drug effects</topic><topic>Scopolamine</topic><topic>Toxicity</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xiao‐Qin</creatorcontrib><creatorcontrib>Zhou, Lu‐Yi</creatorcontrib><creatorcontrib>Tan, Ren‐Xian</creatorcontrib><creatorcontrib>Liang, Guo‐Peng</creatorcontrib><creatorcontrib>Fang, Si‐Xian</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Xie, Mei</creatorcontrib><creatorcontrib>Wen, Yu‐Hao</creatorcontrib><creatorcontrib>Wu, Jia‐Qiang</creatorcontrib><creatorcontrib>Chen, Yi‐Ping</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Chemistry & biodiversity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xiao‐Qin</au><au>Zhou, Lu‐Yi</au><au>Tan, Ren‐Xian</au><au>Liang, Guo‐Peng</au><au>Fang, Si‐Xian</au><au>Li, Wei</au><au>Xie, Mei</au><au>Wen, Yu‐Hao</au><au>Wu, Jia‐Qiang</au><au>Chen, Yi‐Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease</atitle><jtitle>Chemistry & biodiversity</jtitle><addtitle>Chem Biodivers</addtitle><date>2021-11</date><risdate>2021</risdate><volume>18</volume><issue>11</issue><spage>e2100341</spage><epage>n/a</epage><pages>e2100341-n/a</pages><issn>1612-1872</issn><eissn>1612-1880</eissn><abstract>Fifteen chalcone derivatives 3a–3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self‐induced Aβ1‐42 aggregation effectively ranged from 45.9–94.5 % at 20 μM, and acted as potential antioxidants. Their structure‐activity relationships were summarized. In particular, (2E)‐3‐[4‐(dimethylamino)phenyl]‐1‐(pyridin‐2‐yl)prop‐2‐en‐1‐one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 μM, and it could disassemble the self‐induced Aβ1‐42 aggregation fibrils with ratio of 57.1 % at 20 μM concentration. In addition, compound 3g displayed good chelating ability for Cu2+, and could effectively inhibit and disaggregate Cu2+‐induced Aβ aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aβ1‐42‐induced SH‐SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine‐induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy.</abstract><cop>Switzerland</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34510699</pmid><doi>10.1002/cbdv.202100341</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-2563-5048</orcidid></addata></record> |
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| subjects | Agglomeration Alzheimer Disease - drug therapy Alzheimer Disease - metabolism Alzheimer's disease Amyloid beta-Peptides - antagonists & inhibitors Amyloid beta-Peptides - metabolism Animals Antioxidants Aβ aggregation Cell Survival - drug effects chalcone Chalcones - chemical synthesis Chalcones - chemistry Chalcones - pharmacology Chelation Copper Copper - pharmacology Cytotoxicity Drug Design Fibrils Humans Memory Disorders - chemically induced Memory Disorders - drug therapy metal chelating Mice multifunctional Neurodegenerative diseases Neuroprotective Agents - chemical synthesis Neuroprotective Agents - chemistry Neuroprotective Agents - pharmacology Peptide Fragments - antagonists & inhibitors Peptide Fragments - metabolism Protein Aggregates - drug effects Scopolamine Toxicity Tumor Cells, Cultured |
| title | Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease |
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