Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer’s disease brains
There is a high demand for the development of an imaging agent for neurofibrillary tangles (NFTs) detection in Alzheimer’s diagnosis. In the present study, a series of rhodanine-3-acetic acids was synthesized and evaluated for fluorescence imaging of NFTs in brain tissues of AD patients. Five out of...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry 2013-09, Vol.21 (17), p.5139-5144 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5144 |
|---|---|
| container_issue | 17 |
| container_start_page | 5139 |
| container_title | Bioorganic & medicinal chemistry |
| container_volume | 21 |
| creator | Anumala, Upendra Rao Gu, Jiamin Lo Monte, Fabio Kramer, Thomas Heyny-von Haußen, Roland Hölzer, Jana Goetschy-Meyer, Valerie Schön, Christian Mall, Gerhard Hilger, Ingrid Czech, Christian Herms, Jochen Schmidt, Boris |
| description | There is a high demand for the development of an imaging agent for neurofibrillary tangles (NFTs) detection in Alzheimer’s diagnosis. In the present study, a series of rhodanine-3-acetic acids was synthesized and evaluated for fluorescence imaging of NFTs in brain tissues of AD patients. Five out of seven probes have shown excellent binding affinity to NFTs over amyloid plaques in the Thiazine red R displacement assay. However, the selectivity in this in vitro assay is not confirmed by the histopathological evaluation, which indicates significant differences in the binding sites in the assays. Probe 6 showed binding affinity (IC50=19nM) to tau aggregates which is the highest among this series. Probes 2, 3, 4 and 5 display IC50 values of lower than 100nM to tau aggregates to displace Thiazine red R. Evaluation of the cytotoxicity of these five probes with human liver carcinoma cells revealed that these compounds excert negligible cytotoxicity. The in vivo studies with zebrafish embryos confirmed negligible cytotoxicity at 24 and 72h post fertilization. |
| doi_str_mv | 10.1016/j.bmc.2013.06.039 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1419343206</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0968089613005701</els_id><sourcerecordid>1419343206</sourcerecordid><originalsourceid>FETCH-LOGICAL-c377t-f56726f544d6a80e818b61980ce8ff518fc454be97bebfc24d45b625df6a16243</originalsourceid><addsrcrecordid>eNp9kLtuFTEURS0EIjeBD6ABlzQz-DUeW1RRRAJSJApIbflxnPhqxhPsmUhJxW_we3wJjm6gpDrNOlt7L4TeUNJTQuWHfe9m3zNCeU9kT7h-hnZUSNFxrulztCNaqo4oLY_Qca17QggTmr5ER4yrQY8j36F4Pm1Lgeohr7jcLMHmlKHjnfWwJo-tT6Hiu1Q3O6UHwBm2ssTkSpomW-7xavP1BBWnjE-nhxtIM5TfP39VHFIFWwG7YlOur9CLaKcKr5_uCbo6__T97HN3-fXiy9npZef5OK5dHOTIZByECNIqAooqJ6lWxIOKcaAqejEIB3p04KJnIojBSTaEKC2VTPAT9P6Qe1uWHxvU1cypbWtdMyxbNVRQzQVnRDaUHlBflloLRHNb0tw2GUrMo16zN02vedRriDRNb_t5-xS_uRnCv4-_Phvw7gBEuxh7XVI1V99awkAIpZQx0oiPBwKahrsExVSfIHsIqYBfTVjSfwr8AX2gllg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1419343206</pqid></control><display><type>article</type><title>Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer’s disease brains</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Anumala, Upendra Rao ; Gu, Jiamin ; Lo Monte, Fabio ; Kramer, Thomas ; Heyny-von Haußen, Roland ; Hölzer, Jana ; Goetschy-Meyer, Valerie ; Schön, Christian ; Mall, Gerhard ; Hilger, Ingrid ; Czech, Christian ; Herms, Jochen ; Schmidt, Boris</creator><creatorcontrib>Anumala, Upendra Rao ; Gu, Jiamin ; Lo Monte, Fabio ; Kramer, Thomas ; Heyny-von Haußen, Roland ; Hölzer, Jana ; Goetschy-Meyer, Valerie ; Schön, Christian ; Mall, Gerhard ; Hilger, Ingrid ; Czech, Christian ; Herms, Jochen ; Schmidt, Boris</creatorcontrib><description>There is a high demand for the development of an imaging agent for neurofibrillary tangles (NFTs) detection in Alzheimer’s diagnosis. In the present study, a series of rhodanine-3-acetic acids was synthesized and evaluated for fluorescence imaging of NFTs in brain tissues of AD patients. Five out of seven probes have shown excellent binding affinity to NFTs over amyloid plaques in the Thiazine red R displacement assay. However, the selectivity in this in vitro assay is not confirmed by the histopathological evaluation, which indicates significant differences in the binding sites in the assays. Probe 6 showed binding affinity (IC50=19nM) to tau aggregates which is the highest among this series. Probes 2, 3, 4 and 5 display IC50 values of lower than 100nM to tau aggregates to displace Thiazine red R. Evaluation of the cytotoxicity of these five probes with human liver carcinoma cells revealed that these compounds excert negligible cytotoxicity. The in vivo studies with zebrafish embryos confirmed negligible cytotoxicity at 24 and 72h post fertilization.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2013.06.039</identifier><identifier>PMID: 23859773</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Acetates - chemical synthesis ; Acetates - chemistry ; Acetates - toxicity ; acids ; Alzheimer disease ; Alzheimer Disease - metabolism ; Alzheimer Disease - pathology ; Alzheimer’s disease ; amyloid ; Amyloid beta-Peptides - chemistry ; Amyloid beta-Peptides - metabolism ; Animals ; binding capacity ; binding sites ; brain ; Brain - metabolism ; Brain - pathology ; carcinoma ; Cell Line, Tumor ; Cell Survival - drug effects ; Cytotoxicity ; Danio rerio ; Embryo, Nonmammalian - drug effects ; fluorescence ; Fluorescence imaging ; Fluorescent Dyes - chemical synthesis ; Fluorescent Dyes - chemistry ; Fluorescent Dyes - toxicity ; histopathology ; Humans ; image analysis ; in vitro studies ; in vivo studies ; inhibitory concentration 50 ; liver ; Microscopy, Fluorescence ; Neurofibrillary tangles ; patients ; Peptide Fragments - chemistry ; Peptide Fragments - metabolism ; Rhodanine - chemistry ; tau Proteins - chemistry ; tau Proteins - metabolism ; Zebrafish ; Zebrafish - growth & development</subject><ispartof>Bioorganic & medicinal chemistry, 2013-09, Vol.21 (17), p.5139-5144</ispartof><rights>2013 Elsevier Ltd</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-f56726f544d6a80e818b61980ce8ff518fc454be97bebfc24d45b625df6a16243</citedby><cites>FETCH-LOGICAL-c377t-f56726f544d6a80e818b61980ce8ff518fc454be97bebfc24d45b625df6a16243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0968089613005701$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23859773$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anumala, Upendra Rao</creatorcontrib><creatorcontrib>Gu, Jiamin</creatorcontrib><creatorcontrib>Lo Monte, Fabio</creatorcontrib><creatorcontrib>Kramer, Thomas</creatorcontrib><creatorcontrib>Heyny-von Haußen, Roland</creatorcontrib><creatorcontrib>Hölzer, Jana</creatorcontrib><creatorcontrib>Goetschy-Meyer, Valerie</creatorcontrib><creatorcontrib>Schön, Christian</creatorcontrib><creatorcontrib>Mall, Gerhard</creatorcontrib><creatorcontrib>Hilger, Ingrid</creatorcontrib><creatorcontrib>Czech, Christian</creatorcontrib><creatorcontrib>Herms, Jochen</creatorcontrib><creatorcontrib>Schmidt, Boris</creatorcontrib><title>Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer’s disease brains</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>There is a high demand for the development of an imaging agent for neurofibrillary tangles (NFTs) detection in Alzheimer’s diagnosis. In the present study, a series of rhodanine-3-acetic acids was synthesized and evaluated for fluorescence imaging of NFTs in brain tissues of AD patients. Five out of seven probes have shown excellent binding affinity to NFTs over amyloid plaques in the Thiazine red R displacement assay. However, the selectivity in this in vitro assay is not confirmed by the histopathological evaluation, which indicates significant differences in the binding sites in the assays. Probe 6 showed binding affinity (IC50=19nM) to tau aggregates which is the highest among this series. Probes 2, 3, 4 and 5 display IC50 values of lower than 100nM to tau aggregates to displace Thiazine red R. Evaluation of the cytotoxicity of these five probes with human liver carcinoma cells revealed that these compounds excert negligible cytotoxicity. The in vivo studies with zebrafish embryos confirmed negligible cytotoxicity at 24 and 72h post fertilization.</description><subject>Acetates - chemical synthesis</subject><subject>Acetates - chemistry</subject><subject>Acetates - toxicity</subject><subject>acids</subject><subject>Alzheimer disease</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer’s disease</subject><subject>amyloid</subject><subject>Amyloid beta-Peptides - chemistry</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Animals</subject><subject>binding capacity</subject><subject>binding sites</subject><subject>brain</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>carcinoma</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cytotoxicity</subject><subject>Danio rerio</subject><subject>Embryo, Nonmammalian - drug effects</subject><subject>fluorescence</subject><subject>Fluorescence imaging</subject><subject>Fluorescent Dyes - chemical synthesis</subject><subject>Fluorescent Dyes - chemistry</subject><subject>Fluorescent Dyes - toxicity</subject><subject>histopathology</subject><subject>Humans</subject><subject>image analysis</subject><subject>in vitro studies</subject><subject>in vivo studies</subject><subject>inhibitory concentration 50</subject><subject>liver</subject><subject>Microscopy, Fluorescence</subject><subject>Neurofibrillary tangles</subject><subject>patients</subject><subject>Peptide Fragments - chemistry</subject><subject>Peptide Fragments - metabolism</subject><subject>Rhodanine - chemistry</subject><subject>tau Proteins - chemistry</subject><subject>tau Proteins - metabolism</subject><subject>Zebrafish</subject><subject>Zebrafish - growth & development</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kLtuFTEURS0EIjeBD6ABlzQz-DUeW1RRRAJSJApIbflxnPhqxhPsmUhJxW_we3wJjm6gpDrNOlt7L4TeUNJTQuWHfe9m3zNCeU9kT7h-hnZUSNFxrulztCNaqo4oLY_Qca17QggTmr5ER4yrQY8j36F4Pm1Lgeohr7jcLMHmlKHjnfWwJo-tT6Hiu1Q3O6UHwBm2ssTkSpomW-7xavP1BBWnjE-nhxtIM5TfP39VHFIFWwG7YlOur9CLaKcKr5_uCbo6__T97HN3-fXiy9npZef5OK5dHOTIZByECNIqAooqJ6lWxIOKcaAqejEIB3p04KJnIojBSTaEKC2VTPAT9P6Qe1uWHxvU1cypbWtdMyxbNVRQzQVnRDaUHlBflloLRHNb0tw2GUrMo16zN02vedRriDRNb_t5-xS_uRnCv4-_Phvw7gBEuxh7XVI1V99awkAIpZQx0oiPBwKahrsExVSfIHsIqYBfTVjSfwr8AX2gllg</recordid><startdate>20130901</startdate><enddate>20130901</enddate><creator>Anumala, Upendra Rao</creator><creator>Gu, Jiamin</creator><creator>Lo Monte, Fabio</creator><creator>Kramer, Thomas</creator><creator>Heyny-von Haußen, Roland</creator><creator>Hölzer, Jana</creator><creator>Goetschy-Meyer, Valerie</creator><creator>Schön, Christian</creator><creator>Mall, Gerhard</creator><creator>Hilger, Ingrid</creator><creator>Czech, Christian</creator><creator>Herms, Jochen</creator><creator>Schmidt, Boris</creator><general>Elsevier Ltd</general><scope>FBQ</scope><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>7X8</scope></search><sort><creationdate>20130901</creationdate><title>Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer’s disease brains</title><author>Anumala, Upendra Rao ; Gu, Jiamin ; Lo Monte, Fabio ; Kramer, Thomas ; Heyny-von Haußen, Roland ; Hölzer, Jana ; Goetschy-Meyer, Valerie ; Schön, Christian ; Mall, Gerhard ; Hilger, Ingrid ; Czech, Christian ; Herms, Jochen ; Schmidt, Boris</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-f56726f544d6a80e818b61980ce8ff518fc454be97bebfc24d45b625df6a16243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acetates - chemical synthesis</topic><topic>Acetates - chemistry</topic><topic>Acetates - toxicity</topic><topic>acids</topic><topic>Alzheimer disease</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer’s disease</topic><topic>amyloid</topic><topic>Amyloid beta-Peptides - chemistry</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Animals</topic><topic>binding capacity</topic><topic>binding sites</topic><topic>brain</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>carcinoma</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cytotoxicity</topic><topic>Danio rerio</topic><topic>Embryo, Nonmammalian - drug effects</topic><topic>fluorescence</topic><topic>Fluorescence imaging</topic><topic>Fluorescent Dyes - chemical synthesis</topic><topic>Fluorescent Dyes - chemistry</topic><topic>Fluorescent Dyes - toxicity</topic><topic>histopathology</topic><topic>Humans</topic><topic>image analysis</topic><topic>in vitro studies</topic><topic>in vivo studies</topic><topic>inhibitory concentration 50</topic><topic>liver</topic><topic>Microscopy, Fluorescence</topic><topic>Neurofibrillary tangles</topic><topic>patients</topic><topic>Peptide Fragments - chemistry</topic><topic>Peptide Fragments - metabolism</topic><topic>Rhodanine - chemistry</topic><topic>tau Proteins - chemistry</topic><topic>tau Proteins - metabolism</topic><topic>Zebrafish</topic><topic>Zebrafish - growth & development</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anumala, Upendra Rao</creatorcontrib><creatorcontrib>Gu, Jiamin</creatorcontrib><creatorcontrib>Lo Monte, Fabio</creatorcontrib><creatorcontrib>Kramer, Thomas</creatorcontrib><creatorcontrib>Heyny-von Haußen, Roland</creatorcontrib><creatorcontrib>Hölzer, Jana</creatorcontrib><creatorcontrib>Goetschy-Meyer, Valerie</creatorcontrib><creatorcontrib>Schön, Christian</creatorcontrib><creatorcontrib>Mall, Gerhard</creatorcontrib><creatorcontrib>Hilger, Ingrid</creatorcontrib><creatorcontrib>Czech, Christian</creatorcontrib><creatorcontrib>Herms, Jochen</creatorcontrib><creatorcontrib>Schmidt, Boris</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anumala, Upendra Rao</au><au>Gu, Jiamin</au><au>Lo Monte, Fabio</au><au>Kramer, Thomas</au><au>Heyny-von Haußen, Roland</au><au>Hölzer, Jana</au><au>Goetschy-Meyer, Valerie</au><au>Schön, Christian</au><au>Mall, Gerhard</au><au>Hilger, Ingrid</au><au>Czech, Christian</au><au>Herms, Jochen</au><au>Schmidt, Boris</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer’s disease brains</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2013-09-01</date><risdate>2013</risdate><volume>21</volume><issue>17</issue><spage>5139</spage><epage>5144</epage><pages>5139-5144</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>There is a high demand for the development of an imaging agent for neurofibrillary tangles (NFTs) detection in Alzheimer’s diagnosis. In the present study, a series of rhodanine-3-acetic acids was synthesized and evaluated for fluorescence imaging of NFTs in brain tissues of AD patients. Five out of seven probes have shown excellent binding affinity to NFTs over amyloid plaques in the Thiazine red R displacement assay. However, the selectivity in this in vitro assay is not confirmed by the histopathological evaluation, which indicates significant differences in the binding sites in the assays. Probe 6 showed binding affinity (IC50=19nM) to tau aggregates which is the highest among this series. Probes 2, 3, 4 and 5 display IC50 values of lower than 100nM to tau aggregates to displace Thiazine red R. Evaluation of the cytotoxicity of these five probes with human liver carcinoma cells revealed that these compounds excert negligible cytotoxicity. The in vivo studies with zebrafish embryos confirmed negligible cytotoxicity at 24 and 72h post fertilization.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>23859773</pmid><doi>10.1016/j.bmc.2013.06.039</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0968-0896 |
| ispartof | Bioorganic & medicinal chemistry, 2013-09, Vol.21 (17), p.5139-5144 |
| issn | 0968-0896 1464-3391 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1419343206 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Acetates - chemical synthesis Acetates - chemistry Acetates - toxicity acids Alzheimer disease Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer’s disease amyloid Amyloid beta-Peptides - chemistry Amyloid beta-Peptides - metabolism Animals binding capacity binding sites brain Brain - metabolism Brain - pathology carcinoma Cell Line, Tumor Cell Survival - drug effects Cytotoxicity Danio rerio Embryo, Nonmammalian - drug effects fluorescence Fluorescence imaging Fluorescent Dyes - chemical synthesis Fluorescent Dyes - chemistry Fluorescent Dyes - toxicity histopathology Humans image analysis in vitro studies in vivo studies inhibitory concentration 50 liver Microscopy, Fluorescence Neurofibrillary tangles patients Peptide Fragments - chemistry Peptide Fragments - metabolism Rhodanine - chemistry tau Proteins - chemistry tau Proteins - metabolism Zebrafish Zebrafish - growth & development |
| title | Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer’s disease brains |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T18%3A41%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fluorescent%20rhodanine-3-acetic%20acids%20visualize%20neurofibrillary%20tangles%20in%20Alzheimer%E2%80%99s%20disease%20brains&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry&rft.au=Anumala,%20Upendra%20Rao&rft.date=2013-09-01&rft.volume=21&rft.issue=17&rft.spage=5139&rft.epage=5144&rft.pages=5139-5144&rft.issn=0968-0896&rft.eissn=1464-3391&rft_id=info:doi/10.1016/j.bmc.2013.06.039&rft_dat=%3Cproquest_cross%3E1419343206%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1419343206&rft_id=info:pmid/23859773&rft_els_id=S0968089613005701&rfr_iscdi=true |