Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities
[Display omitted] New pharmaceutically active compounds can be obtained by modification of existing drugs to access more effective agents in the wake of drug resistance amongst others. To achieve this goal the concept of hybridization was established during the last decade. We employed this concept...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2015-09, Vol.23 (17), p.5452-5458 |
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| container_title | Bioorganic & medicinal chemistry |
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| creator | Reiter, Christoph Fröhlich, Tony Gruber, Lisa Hutterer, Corina Marschall, Manfred Voigtländer, Cornelia Friedrich, Oliver Kappes, Barbara Efferth, Thomas Tsogoeva, Svetlana B. |
| description | [Display omitted]
New pharmaceutically active compounds can be obtained by modification of existing drugs to access more effective agents in the wake of drug resistance amongst others. To achieve this goal the concept of hybridization was established during the last decade. We employed this concept by coupling two artemisinin-derived precursors to obtain dimers or trimers with increased in vitro activity against Plasmodiumfalciparum 3D7 strain, leukemia cells (CCRF-CEM and multidrug-resistant subline CEM/ADR5000) and human cytomegalovirus (HCMV). Dimer 4 (IC50 of 2.6nM) possess superior antimalarial activity compared with its parent compound artesunic acid(3) (IC50 of 9.0nM). Dimer5 and trimers6 and 7 display superior potency against both leukemia cell lines (IC50 up to 0.002μM for CCRF-CEM and IC50 up to 0.20μM for CEM/ADR5000) and are even more active than clinically used doxorubicin (IC50 1.61μM for CEM/ADR5000). With respect to anti-HCMV activity, trimer6 is the most efficient hybrid (IC50 0.04μM) outperforming ganciclovir (IC50 2.6μM), dihydroartemisinin(IC50 >10μM) and artesunic acid (IC50 3.8μM). |
| doi_str_mv | 10.1016/j.bmc.2015.07.048 |
| format | Article |
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New pharmaceutically active compounds can be obtained by modification of existing drugs to access more effective agents in the wake of drug resistance amongst others. To achieve this goal the concept of hybridization was established during the last decade. We employed this concept by coupling two artemisinin-derived precursors to obtain dimers or trimers with increased in vitro activity against Plasmodiumfalciparum 3D7 strain, leukemia cells (CCRF-CEM and multidrug-resistant subline CEM/ADR5000) and human cytomegalovirus (HCMV). Dimer 4 (IC50 of 2.6nM) possess superior antimalarial activity compared with its parent compound artesunic acid(3) (IC50 of 9.0nM). Dimer5 and trimers6 and 7 display superior potency against both leukemia cell lines (IC50 up to 0.002μM for CCRF-CEM and IC50 up to 0.20μM for CEM/ADR5000) and are even more active than clinically used doxorubicin (IC50 1.61μM for CEM/ADR5000). With respect to anti-HCMV activity, trimer6 is the most efficient hybrid (IC50 0.04μM) outperforming ganciclovir (IC50 2.6μM), dihydroartemisinin(IC50 >10μM) and artesunic acid (IC50 3.8μM).</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2015.07.048</identifier><identifier>PMID: 26260339</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anticancer activity ; Antimalarial activity ; Antimalarials - pharmacology ; Antineoplastic Agents, Phytogenic - pharmacology ; Antiviral activity ; Antiviral Agents - pharmacology ; Artemisinin-derived dimers ; Artemisinin-derived hybrids ; Artemisinin-derived trimers ; Artemisinins - administration & dosage ; Artemisinins - pharmacology ; Artemisinins - therapeutic use ; Humans ; Molecular Structure</subject><ispartof>Bioorganic & medicinal chemistry, 2015-09, Vol.23 (17), p.5452-5458</ispartof><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-345bd085a9557c2701c0f312f85889f4627cf1d56e4aa2bcc035c5d46f70e3473</citedby><cites>FETCH-LOGICAL-c423t-345bd085a9557c2701c0f312f85889f4627cf1d56e4aa2bcc035c5d46f70e3473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S096808961500632X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26260339$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reiter, Christoph</creatorcontrib><creatorcontrib>Fröhlich, Tony</creatorcontrib><creatorcontrib>Gruber, Lisa</creatorcontrib><creatorcontrib>Hutterer, Corina</creatorcontrib><creatorcontrib>Marschall, Manfred</creatorcontrib><creatorcontrib>Voigtländer, Cornelia</creatorcontrib><creatorcontrib>Friedrich, Oliver</creatorcontrib><creatorcontrib>Kappes, Barbara</creatorcontrib><creatorcontrib>Efferth, Thomas</creatorcontrib><creatorcontrib>Tsogoeva, Svetlana B.</creatorcontrib><title>Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>[Display omitted]
New pharmaceutically active compounds can be obtained by modification of existing drugs to access more effective agents in the wake of drug resistance amongst others. To achieve this goal the concept of hybridization was established during the last decade. We employed this concept by coupling two artemisinin-derived precursors to obtain dimers or trimers with increased in vitro activity against Plasmodiumfalciparum 3D7 strain, leukemia cells (CCRF-CEM and multidrug-resistant subline CEM/ADR5000) and human cytomegalovirus (HCMV). Dimer 4 (IC50 of 2.6nM) possess superior antimalarial activity compared with its parent compound artesunic acid(3) (IC50 of 9.0nM). Dimer5 and trimers6 and 7 display superior potency against both leukemia cell lines (IC50 up to 0.002μM for CCRF-CEM and IC50 up to 0.20μM for CEM/ADR5000) and are even more active than clinically used doxorubicin (IC50 1.61μM for CEM/ADR5000). With respect to anti-HCMV activity, trimer6 is the most efficient hybrid (IC50 0.04μM) outperforming ganciclovir (IC50 2.6μM), dihydroartemisinin(IC50 >10μM) and artesunic acid (IC50 3.8μM).</description><subject>Anticancer activity</subject><subject>Antimalarial activity</subject><subject>Antimalarials - pharmacology</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Antiviral activity</subject><subject>Antiviral Agents - pharmacology</subject><subject>Artemisinin-derived dimers</subject><subject>Artemisinin-derived hybrids</subject><subject>Artemisinin-derived trimers</subject><subject>Artemisinins - administration & dosage</subject><subject>Artemisinins - pharmacology</subject><subject>Artemisinins - therapeutic use</subject><subject>Humans</subject><subject>Molecular Structure</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UcFu1DAQtRCILoUP4IJ85NCEsWM7CZyqqrRIlXoAzpbXnlAvTrLYzkr7Df1pvLstR04z8-a9J808Qt4zqBkw9WlTr0dbc2CyhrYG0b0gKyaUqJqmZy_JCnrVVdD16oy8SWkDAFz07DU544orKKQVebz1vx7Cnm7njFOmJmYcffKTnyqH0e_QUedHjImaydEcj_1n-n0_5QdM_gTjzoTFZD9PdB5oWfhY8OxHE0z0Jlwcp4DL72JujpIDsPPRBGrsocse01vyajAh4bunek5-fr3-cXVb3d3ffLu6vKus4E2uGiHXDjppeilby1tgFoaG8aGTXdcPQvHWDsxJhcIYvrYWGmmlE2poARvRNufk48l3G-c_C6asy8kWQzATzkvSrIViJDsuC5WdqDbOKUUc9La8wMS9ZqAPGeiNLhnoQwYaWl0yKJoPT_bLekT3T_H89EL4ciJgOXLnMepkPU4WnY9os3az_4_9X_jHmg4</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Reiter, Christoph</creator><creator>Fröhlich, Tony</creator><creator>Gruber, Lisa</creator><creator>Hutterer, Corina</creator><creator>Marschall, Manfred</creator><creator>Voigtländer, Cornelia</creator><creator>Friedrich, Oliver</creator><creator>Kappes, Barbara</creator><creator>Efferth, Thomas</creator><creator>Tsogoeva, Svetlana B.</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>20150901</creationdate><title>Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities</title><author>Reiter, Christoph ; Fröhlich, Tony ; Gruber, Lisa ; Hutterer, Corina ; Marschall, Manfred ; Voigtländer, Cornelia ; Friedrich, Oliver ; Kappes, Barbara ; Efferth, Thomas ; Tsogoeva, Svetlana B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-345bd085a9557c2701c0f312f85889f4627cf1d56e4aa2bcc035c5d46f70e3473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Anticancer activity</topic><topic>Antimalarial activity</topic><topic>Antimalarials - pharmacology</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Antiviral activity</topic><topic>Antiviral Agents - pharmacology</topic><topic>Artemisinin-derived dimers</topic><topic>Artemisinin-derived hybrids</topic><topic>Artemisinin-derived trimers</topic><topic>Artemisinins - administration & dosage</topic><topic>Artemisinins - pharmacology</topic><topic>Artemisinins - therapeutic use</topic><topic>Humans</topic><topic>Molecular Structure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reiter, Christoph</creatorcontrib><creatorcontrib>Fröhlich, Tony</creatorcontrib><creatorcontrib>Gruber, Lisa</creatorcontrib><creatorcontrib>Hutterer, Corina</creatorcontrib><creatorcontrib>Marschall, Manfred</creatorcontrib><creatorcontrib>Voigtländer, Cornelia</creatorcontrib><creatorcontrib>Friedrich, Oliver</creatorcontrib><creatorcontrib>Kappes, Barbara</creatorcontrib><creatorcontrib>Efferth, Thomas</creatorcontrib><creatorcontrib>Tsogoeva, Svetlana B.</creatorcontrib><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>Reiter, Christoph</au><au>Fröhlich, Tony</au><au>Gruber, Lisa</au><au>Hutterer, Corina</au><au>Marschall, Manfred</au><au>Voigtländer, Cornelia</au><au>Friedrich, Oliver</au><au>Kappes, Barbara</au><au>Efferth, Thomas</au><au>Tsogoeva, Svetlana B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>23</volume><issue>17</issue><spage>5452</spage><epage>5458</epage><pages>5452-5458</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>[Display omitted]
New pharmaceutically active compounds can be obtained by modification of existing drugs to access more effective agents in the wake of drug resistance amongst others. To achieve this goal the concept of hybridization was established during the last decade. We employed this concept by coupling two artemisinin-derived precursors to obtain dimers or trimers with increased in vitro activity against Plasmodiumfalciparum 3D7 strain, leukemia cells (CCRF-CEM and multidrug-resistant subline CEM/ADR5000) and human cytomegalovirus (HCMV). Dimer 4 (IC50 of 2.6nM) possess superior antimalarial activity compared with its parent compound artesunic acid(3) (IC50 of 9.0nM). Dimer5 and trimers6 and 7 display superior potency against both leukemia cell lines (IC50 up to 0.002μM for CCRF-CEM and IC50 up to 0.20μM for CEM/ADR5000) and are even more active than clinically used doxorubicin (IC50 1.61μM for CEM/ADR5000). With respect to anti-HCMV activity, trimer6 is the most efficient hybrid (IC50 0.04μM) outperforming ganciclovir (IC50 2.6μM), dihydroartemisinin(IC50 >10μM) and artesunic acid (IC50 3.8μM).</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>26260339</pmid><doi>10.1016/j.bmc.2015.07.048</doi><tpages>7</tpages></addata></record> |
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| subjects | Anticancer activity Antimalarial activity Antimalarials - pharmacology Antineoplastic Agents, Phytogenic - pharmacology Antiviral activity Antiviral Agents - pharmacology Artemisinin-derived dimers Artemisinin-derived hybrids Artemisinin-derived trimers Artemisinins - administration & dosage Artemisinins - pharmacology Artemisinins - therapeutic use Humans Molecular Structure |
| title | Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities |
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