Semisynthetic 15-O-acyl- and 1, 15-Di-O-acyleurycomanones from Eurycoma longifolia as potential antimalarials
Abstract Among the quassinoids isolated from EURYCOMA LONGIFOLIA Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of PLASMODIUM FALCIPARUM. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-...
Gespeichert in:
| Veröffentlicht in: | Planta medica 2005-10, Vol.71 (10), p.967-969 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 969 |
|---|---|
| container_issue | 10 |
| container_start_page | 967 |
| container_title | Planta medica |
| container_volume | 71 |
| creator | Chan, K.L Choo, C.Y Abdullah, N.R |
| description | Abstract
Among the quassinoids isolated from EURYCOMA LONGIFOLIA Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of PLASMODIUM FALCIPARUM. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-O-(3,3-dimethylacryloyl)- eurycomanone and 1,15-di-O-benzoyleurycomanone were synthesized by direct acylation with the respective acid chlorides. The monoacylated 15-O-isovaleryleurycomanone was synthesized by selective protection of the other hydroxy groups of eurycomanone with trimethylsilyl trifluoromethanesulphonate to enable the exclusive acylation of its C-15 hydroxy group. This was followed by the removal of the protecting groups with citric acid. The diacylated eurycomanones exhibited lower antiplasmodial activity against the Gombak A isolates and lower toxicity in the brine shrimp assay when compared to eurycomanone. In contrast, the monoacylated derivative displayed comparable antiplasmodial potency to eurycomanone, but its toxicity was reduced. Thus, preliminary studies of the synthesized acylated eurycomanones have shown that acylation only at the C-15 hydroxy group may be worthy of further antimalarial investigation. |
| doi_str_mv | 10.1055/s-2005-864188 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1055_s_2005_864188</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>16254833</sourcerecordid><originalsourceid>FETCH-LOGICAL-c382t-23c5c5b4e27918d60fb58aced6b50d39082b7bfc24581edaac273fc4dfd71fbc3</originalsourceid><addsrcrecordid>eNp1kDtPwzAUhS0EgvIYWSELWw3Xr8QZUSkPCakDMEeOY7dGSVzZ6dB_j6tE6sR0dY8-nXvuQeiWwCMBIZ4ipgACy5wTKU_QjHBWYqCUnKIZAKMYSs4u0GWMvwCElwDn6ILkVHDJ2Ax1X6Zzcd8PGzM4nRGBV1jpfYsz1TcZmR-UFzeJZhf22neq972JmQ2-y5aTlLW-XzvrW6cyFbOtH0w_ONUmm8F1qlUhLfEandk0zM00r9DP6_J78Y4_V28fi-dPrJmkA6ZMCy1qbmhREtnkYGshlTZNXgtoWAmS1kVtNeVCEtMopWnBrOaNbQpia82uEB59dfAxBmOrbUgpwr4iUB1qq2J1qK0aa0v83chvd3VnmiM99ZSAhwlQUavWBtVrF49ckQLIUiRuPnLDxpnOVL9-F_r06b9370fcKl-pdUiWP18UCAMCPJeQsz-fPozS</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Semisynthetic 15-O-acyl- and 1, 15-Di-O-acyleurycomanones from Eurycoma longifolia as potential antimalarials</title><source>MEDLINE</source><source>Thieme Connect Journals</source><creator>Chan, K.L ; Choo, C.Y ; Abdullah, N.R</creator><creatorcontrib>Chan, K.L ; Choo, C.Y ; Abdullah, N.R</creatorcontrib><description>Abstract
Among the quassinoids isolated from EURYCOMA LONGIFOLIA Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of PLASMODIUM FALCIPARUM. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-O-(3,3-dimethylacryloyl)- eurycomanone and 1,15-di-O-benzoyleurycomanone were synthesized by direct acylation with the respective acid chlorides. The monoacylated 15-O-isovaleryleurycomanone was synthesized by selective protection of the other hydroxy groups of eurycomanone with trimethylsilyl trifluoromethanesulphonate to enable the exclusive acylation of its C-15 hydroxy group. This was followed by the removal of the protecting groups with citric acid. The diacylated eurycomanones exhibited lower antiplasmodial activity against the Gombak A isolates and lower toxicity in the brine shrimp assay when compared to eurycomanone. In contrast, the monoacylated derivative displayed comparable antiplasmodial potency to eurycomanone, but its toxicity was reduced. Thus, preliminary studies of the synthesized acylated eurycomanones have shown that acylation only at the C-15 hydroxy group may be worthy of further antimalarial investigation.</description><identifier>ISSN: 0032-0943</identifier><identifier>EISSN: 1439-0221</identifier><identifier>DOI: 10.1055/s-2005-864188</identifier><identifier>PMID: 16254833</identifier><identifier>CODEN: PLMEAA</identifier><language>eng</language><publisher>Stuttgart: Thieme</publisher><subject>acyleurycomanone ; Animals ; antimalarials ; Antimalarials - administration & dosage ; Antimalarials - chemical synthesis ; Antimalarials - pharmacology ; Antimalarials - therapeutic use ; Artemia - drug effects ; Artemia salina ; Biological and medical sciences ; Chloroquine ; Drug Resistance ; Eurycoma ; Eurycoma longifolia ; eurycomanone ; General pharmacology ; human health ; Humans ; isovaleryleurycomanone ; Letter ; Malaria, Falciparum - drug therapy ; Medical sciences ; medicinal plants ; Parasitic Sensitivity Tests ; Pharmacognosy. Homeopathy. Health food ; Pharmacology. Drug treatments ; phytochemicals ; Phytotherapy ; plant extracts ; Plant Extracts - administration & dosage ; Plant Extracts - chemical synthesis ; Plant Extracts - pharmacology ; Plant Extracts - therapeutic use ; Plant Roots ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; quassinoids ; toxicity testing ; traditional medicine ; triterpenoids</subject><ispartof>Planta medica, 2005-10, Vol.71 (10), p.967-969</ispartof><rights>Georg Thieme Verlag KG Stuttgart · New York</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-23c5c5b4e27918d60fb58aced6b50d39082b7bfc24581edaac273fc4dfd71fbc3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-2005-864188.pdf$$EPDF$$P50$$Gthieme$$H</linktopdf><linktohtml>$$Uhttps://www.thieme-connect.de/products/ejournals/html/10.1055/s-2005-864188$$EHTML$$P50$$Gthieme$$H</linktohtml><link.rule.ids>314,780,784,3015,3016,27923,27924,54558,54559</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17273895$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16254833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chan, K.L</creatorcontrib><creatorcontrib>Choo, C.Y</creatorcontrib><creatorcontrib>Abdullah, N.R</creatorcontrib><title>Semisynthetic 15-O-acyl- and 1, 15-Di-O-acyleurycomanones from Eurycoma longifolia as potential antimalarials</title><title>Planta medica</title><addtitle>Planta Med</addtitle><description>Abstract
Among the quassinoids isolated from EURYCOMA LONGIFOLIA Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of PLASMODIUM FALCIPARUM. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-O-(3,3-dimethylacryloyl)- eurycomanone and 1,15-di-O-benzoyleurycomanone were synthesized by direct acylation with the respective acid chlorides. The monoacylated 15-O-isovaleryleurycomanone was synthesized by selective protection of the other hydroxy groups of eurycomanone with trimethylsilyl trifluoromethanesulphonate to enable the exclusive acylation of its C-15 hydroxy group. This was followed by the removal of the protecting groups with citric acid. The diacylated eurycomanones exhibited lower antiplasmodial activity against the Gombak A isolates and lower toxicity in the brine shrimp assay when compared to eurycomanone. In contrast, the monoacylated derivative displayed comparable antiplasmodial potency to eurycomanone, but its toxicity was reduced. Thus, preliminary studies of the synthesized acylated eurycomanones have shown that acylation only at the C-15 hydroxy group may be worthy of further antimalarial investigation.</description><subject>acyleurycomanone</subject><subject>Animals</subject><subject>antimalarials</subject><subject>Antimalarials - administration & dosage</subject><subject>Antimalarials - chemical synthesis</subject><subject>Antimalarials - pharmacology</subject><subject>Antimalarials - therapeutic use</subject><subject>Artemia - drug effects</subject><subject>Artemia salina</subject><subject>Biological and medical sciences</subject><subject>Chloroquine</subject><subject>Drug Resistance</subject><subject>Eurycoma</subject><subject>Eurycoma longifolia</subject><subject>eurycomanone</subject><subject>General pharmacology</subject><subject>human health</subject><subject>Humans</subject><subject>isovaleryleurycomanone</subject><subject>Letter</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Medical sciences</subject><subject>medicinal plants</subject><subject>Parasitic Sensitivity Tests</subject><subject>Pharmacognosy. Homeopathy. Health food</subject><subject>Pharmacology. Drug treatments</subject><subject>phytochemicals</subject><subject>Phytotherapy</subject><subject>plant extracts</subject><subject>Plant Extracts - administration & dosage</subject><subject>Plant Extracts - chemical synthesis</subject><subject>Plant Extracts - pharmacology</subject><subject>Plant Extracts - therapeutic use</subject><subject>Plant Roots</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>quassinoids</subject><subject>toxicity testing</subject><subject>traditional medicine</subject><subject>triterpenoids</subject><issn>0032-0943</issn><issn>1439-0221</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kDtPwzAUhS0EgvIYWSELWw3Xr8QZUSkPCakDMEeOY7dGSVzZ6dB_j6tE6sR0dY8-nXvuQeiWwCMBIZ4ipgACy5wTKU_QjHBWYqCUnKIZAKMYSs4u0GWMvwCElwDn6ILkVHDJ2Ax1X6Zzcd8PGzM4nRGBV1jpfYsz1TcZmR-UFzeJZhf22neq972JmQ2-y5aTlLW-XzvrW6cyFbOtH0w_ONUmm8F1qlUhLfEandk0zM00r9DP6_J78Y4_V28fi-dPrJmkA6ZMCy1qbmhREtnkYGshlTZNXgtoWAmS1kVtNeVCEtMopWnBrOaNbQpia82uEB59dfAxBmOrbUgpwr4iUB1qq2J1qK0aa0v83chvd3VnmiM99ZSAhwlQUavWBtVrF49ckQLIUiRuPnLDxpnOVL9-F_r06b9370fcKl-pdUiWP18UCAMCPJeQsz-fPozS</recordid><startdate>20051001</startdate><enddate>20051001</enddate><creator>Chan, K.L</creator><creator>Choo, C.Y</creator><creator>Abdullah, N.R</creator><general>Thieme</general><scope>FBQ</scope><scope>IQODW</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></search><sort><creationdate>20051001</creationdate><title>Semisynthetic 15-O-acyl- and 1, 15-Di-O-acyleurycomanones from Eurycoma longifolia as potential antimalarials</title><author>Chan, K.L ; Choo, C.Y ; Abdullah, N.R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-23c5c5b4e27918d60fb58aced6b50d39082b7bfc24581edaac273fc4dfd71fbc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>acyleurycomanone</topic><topic>Animals</topic><topic>antimalarials</topic><topic>Antimalarials - administration & dosage</topic><topic>Antimalarials - chemical synthesis</topic><topic>Antimalarials - pharmacology</topic><topic>Antimalarials - therapeutic use</topic><topic>Artemia - drug effects</topic><topic>Artemia salina</topic><topic>Biological and medical sciences</topic><topic>Chloroquine</topic><topic>Drug Resistance</topic><topic>Eurycoma</topic><topic>Eurycoma longifolia</topic><topic>eurycomanone</topic><topic>General pharmacology</topic><topic>human health</topic><topic>Humans</topic><topic>isovaleryleurycomanone</topic><topic>Letter</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Medical sciences</topic><topic>medicinal plants</topic><topic>Parasitic Sensitivity Tests</topic><topic>Pharmacognosy. Homeopathy. Health food</topic><topic>Pharmacology. Drug treatments</topic><topic>phytochemicals</topic><topic>Phytotherapy</topic><topic>plant extracts</topic><topic>Plant Extracts - administration & dosage</topic><topic>Plant Extracts - chemical synthesis</topic><topic>Plant Extracts - pharmacology</topic><topic>Plant Extracts - therapeutic use</topic><topic>Plant Roots</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - drug effects</topic><topic>quassinoids</topic><topic>toxicity testing</topic><topic>traditional medicine</topic><topic>triterpenoids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chan, K.L</creatorcontrib><creatorcontrib>Choo, C.Y</creatorcontrib><creatorcontrib>Abdullah, N.R</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Planta medica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chan, K.L</au><au>Choo, C.Y</au><au>Abdullah, N.R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Semisynthetic 15-O-acyl- and 1, 15-Di-O-acyleurycomanones from Eurycoma longifolia as potential antimalarials</atitle><jtitle>Planta medica</jtitle><addtitle>Planta Med</addtitle><date>2005-10-01</date><risdate>2005</risdate><volume>71</volume><issue>10</issue><spage>967</spage><epage>969</epage><pages>967-969</pages><issn>0032-0943</issn><eissn>1439-0221</eissn><coden>PLMEAA</coden><abstract>Abstract
Among the quassinoids isolated from EURYCOMA LONGIFOLIA Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of PLASMODIUM FALCIPARUM. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-O-(3,3-dimethylacryloyl)- eurycomanone and 1,15-di-O-benzoyleurycomanone were synthesized by direct acylation with the respective acid chlorides. The monoacylated 15-O-isovaleryleurycomanone was synthesized by selective protection of the other hydroxy groups of eurycomanone with trimethylsilyl trifluoromethanesulphonate to enable the exclusive acylation of its C-15 hydroxy group. This was followed by the removal of the protecting groups with citric acid. The diacylated eurycomanones exhibited lower antiplasmodial activity against the Gombak A isolates and lower toxicity in the brine shrimp assay when compared to eurycomanone. In contrast, the monoacylated derivative displayed comparable antiplasmodial potency to eurycomanone, but its toxicity was reduced. Thus, preliminary studies of the synthesized acylated eurycomanones have shown that acylation only at the C-15 hydroxy group may be worthy of further antimalarial investigation.</abstract><cop>Stuttgart</cop><cop>New York, NY</cop><pub>Thieme</pub><pmid>16254833</pmid><doi>10.1055/s-2005-864188</doi><tpages>3</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0032-0943 |
| ispartof | Planta medica, 2005-10, Vol.71 (10), p.967-969 |
| issn | 0032-0943 1439-0221 |
| language | eng |
| recordid | cdi_crossref_primary_10_1055_s_2005_864188 |
| source | MEDLINE; Thieme Connect Journals |
| subjects | acyleurycomanone Animals antimalarials Antimalarials - administration & dosage Antimalarials - chemical synthesis Antimalarials - pharmacology Antimalarials - therapeutic use Artemia - drug effects Artemia salina Biological and medical sciences Chloroquine Drug Resistance Eurycoma Eurycoma longifolia eurycomanone General pharmacology human health Humans isovaleryleurycomanone Letter Malaria, Falciparum - drug therapy Medical sciences medicinal plants Parasitic Sensitivity Tests Pharmacognosy. Homeopathy. Health food Pharmacology. Drug treatments phytochemicals Phytotherapy plant extracts Plant Extracts - administration & dosage Plant Extracts - chemical synthesis Plant Extracts - pharmacology Plant Extracts - therapeutic use Plant Roots Plasmodium falciparum Plasmodium falciparum - drug effects quassinoids toxicity testing traditional medicine triterpenoids |
| title | Semisynthetic 15-O-acyl- and 1, 15-Di-O-acyleurycomanones from Eurycoma longifolia as potential antimalarials |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T23%3A31%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Semisynthetic%2015-O-acyl-%20and%201,%2015-Di-O-acyleurycomanones%20from%20Eurycoma%20longifolia%20as%20potential%20antimalarials&rft.jtitle=Planta%20medica&rft.au=Chan,%20K.L&rft.date=2005-10-01&rft.volume=71&rft.issue=10&rft.spage=967&rft.epage=969&rft.pages=967-969&rft.issn=0032-0943&rft.eissn=1439-0221&rft.coden=PLMEAA&rft_id=info:doi/10.1055/s-2005-864188&rft_dat=%3Cpubmed_cross%3E16254833%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/16254833&rfr_iscdi=true |