Antimalarial Activity of Crambescidin 800 and Synthetic Analogues against Liver and Blood Stage of Plasmodium sp
Structural features associated with the antimalarial activity of the marine natural product crambescidin 800 were studied using synthetic analogues of the related compound ptilomycalin A. The study suggests that the guanidine moiety is cytotoxic, whereas the spermidine-containing aliphatic chain inc...
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| Veröffentlicht in: | Journal of antibiotics 2006-09, Vol.59 (9), p.583-590 |
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| creator | Lazaro, J Enrico H Nitcheu, Josiane Mahmoudi, Nassira Ibana, Joyce A Mangalindan, Gina C Black, Gregory P Howard-Jones, Andrew G Moore, Christopher G Thomas, Dafydd A Mazier, Dominique Ireland, Chris M Concepcion, Gisela P Murphy, Patrick J Diquet, Bertrand |
| description | Structural features associated with the antimalarial activity of the marine natural product crambescidin 800 were studied using synthetic analogues of the related compound ptilomycalin A. The study suggests that the guanidine moiety is cytotoxic, whereas the spermidine-containing aliphatic chain increases activity. The most active analogue, compound
11
, had
in vitro
activity against
Plasmodium falciparum
strain 3D7 (IC
50
=490 nM) that was stronger than the
in vitro
activity against murine L5178Y cells (IC
50
=8.5~59 μM).
In vitro
growth inhibition of liver stages of
P. yoelii yoelii
in mouse hepatocytes was observed (IC
50
=9.2 μM). The compound did not significantly prolong median survival time after a single subcutaneous administration of 80 mg/kg in
P. berghei
-infected mice. Compound
11
did not cause DNA fragmentation in an
in vitro
micronucleus assay. |
| doi_str_mv | 10.1038/ja.2006.78 |
| format | Article |
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11
, had
in vitro
activity against
Plasmodium falciparum
strain 3D7 (IC
50
=490 nM) that was stronger than the
in vitro
activity against murine L5178Y cells (IC
50
=8.5~59 μM).
In vitro
growth inhibition of liver stages of
P. yoelii yoelii
in mouse hepatocytes was observed (IC
50
=9.2 μM). The compound did not significantly prolong median survival time after a single subcutaneous administration of 80 mg/kg in
P. berghei
-infected mice. Compound
11
did not cause DNA fragmentation in an
in vitro
micronucleus assay.</description><identifier>ISSN: 0021-8820</identifier><identifier>EISSN: 1881-1469</identifier><identifier>DOI: 10.1038/ja.2006.78</identifier><identifier>PMID: 17136890</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Antimalarials - chemistry ; Antimalarials - pharmacology ; Antimalarials - toxicity ; Bacteriology ; Biomedical and Life Sciences ; Bioorganic Chemistry ; Cells, Cultured ; Disease Models, Animal ; Erythrocytes - parasitology ; Guanidine - analogs & derivatives ; Guanidine - chemistry ; Guanidine - pharmacology ; Guanidine - toxicity ; Hepatocytes - parasitology ; Life Sciences ; Malaria - drug therapy ; Medicinal Chemistry ; Mice ; Microbiology ; Molecular Structure ; Organic Chemistry ; Parasitic Sensitivity Tests ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium yoelii - drug effects ; Spiro Compounds - chemistry ; Spiro Compounds - pharmacology ; Spiro Compounds - toxicity ; Survival Analysis</subject><ispartof>Journal of antibiotics, 2006-09, Vol.59 (9), p.583-590</ispartof><rights>Japan Antibiotics Research Association 2006</rights><rights>Copyright Nature Publishing Group Sep 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c469t-e5211656cd3820b189af7c471dce0fceaaee6c43d5226358db4f5f2e330967fb3</citedby><cites>FETCH-LOGICAL-c469t-e5211656cd3820b189af7c471dce0fceaaee6c43d5226358db4f5f2e330967fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17136890$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lazaro, J Enrico H</creatorcontrib><creatorcontrib>Nitcheu, Josiane</creatorcontrib><creatorcontrib>Mahmoudi, Nassira</creatorcontrib><creatorcontrib>Ibana, Joyce A</creatorcontrib><creatorcontrib>Mangalindan, Gina C</creatorcontrib><creatorcontrib>Black, Gregory P</creatorcontrib><creatorcontrib>Howard-Jones, Andrew G</creatorcontrib><creatorcontrib>Moore, Christopher G</creatorcontrib><creatorcontrib>Thomas, Dafydd A</creatorcontrib><creatorcontrib>Mazier, Dominique</creatorcontrib><creatorcontrib>Ireland, Chris M</creatorcontrib><creatorcontrib>Concepcion, Gisela P</creatorcontrib><creatorcontrib>Murphy, Patrick J</creatorcontrib><creatorcontrib>Diquet, Bertrand</creatorcontrib><title>Antimalarial Activity of Crambescidin 800 and Synthetic Analogues against Liver and Blood Stage of Plasmodium sp</title><title>Journal of antibiotics</title><addtitle>J Antibiot</addtitle><addtitle>J Antibiot (Tokyo)</addtitle><description>Structural features associated with the antimalarial activity of the marine natural product crambescidin 800 were studied using synthetic analogues of the related compound ptilomycalin A. The study suggests that the guanidine moiety is cytotoxic, whereas the spermidine-containing aliphatic chain increases activity. The most active analogue, compound
11
, had
in vitro
activity against
Plasmodium falciparum
strain 3D7 (IC
50
=490 nM) that was stronger than the
in vitro
activity against murine L5178Y cells (IC
50
=8.5~59 μM).
In vitro
growth inhibition of liver stages of
P. yoelii yoelii
in mouse hepatocytes was observed (IC
50
=9.2 μM). The compound did not significantly prolong median survival time after a single subcutaneous administration of 80 mg/kg in
P. berghei
-infected mice. Compound
11
did not cause DNA fragmentation in an
in vitro
micronucleus assay.</description><subject>Animals</subject><subject>Antimalarials - chemistry</subject><subject>Antimalarials - pharmacology</subject><subject>Antimalarials - toxicity</subject><subject>Bacteriology</subject><subject>Biomedical and Life Sciences</subject><subject>Bioorganic Chemistry</subject><subject>Cells, Cultured</subject><subject>Disease Models, Animal</subject><subject>Erythrocytes - parasitology</subject><subject>Guanidine - analogs & derivatives</subject><subject>Guanidine - chemistry</subject><subject>Guanidine - pharmacology</subject><subject>Guanidine - toxicity</subject><subject>Hepatocytes - parasitology</subject><subject>Life Sciences</subject><subject>Malaria - drug therapy</subject><subject>Medicinal Chemistry</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Molecular Structure</subject><subject>Organic Chemistry</subject><subject>Parasitic Sensitivity Tests</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium yoelii - drug effects</subject><subject>Spiro Compounds - chemistry</subject><subject>Spiro Compounds - pharmacology</subject><subject>Spiro Compounds - toxicity</subject><subject>Survival Analysis</subject><issn>0021-8820</issn><issn>1881-1469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpl0V1r2zAUBmAxNtqs7c1-wBAMerHhTB-2JF-mYV8Q2GDttTmWjzMF28okuZB_X6UJbGxXutDDq1fnEPKGsyVn0nzcwVIwppbavCALbgwveKnql2TBmOCFMYJdktcx7hiTWmpzQS655lKZmi3IfjUlN8IAwcFAVza5R5cO1Pd0HWBsMVrXuYkaxihMHf15mNIvTM7S1QSD384YKWzBTTHRjXvE8KzuBu-zTbDFY9KPAeLoOzePNO6vyasehog35_OKPHz-dL_-Wmy-f_m2Xm0Km7unAivBuaqU7WTu33JTQ69tqXlnkfUWARCVLWVXCaFkZbq27KteoJSsVrpv5RW5PeXug_-da6ZmdNHiMMCEfo4Nr5Uqq1pl-O4fuPNzyL_LRhttuKhEldX7k7LBxxiwb_Yhzy0cGs6a4xaaHTTHLTTaZPz2HDm3I3Z_6HnsGXw4gZivpi2Gv978P-4JUruQPw</recordid><startdate>20060901</startdate><enddate>20060901</enddate><creator>Lazaro, J Enrico H</creator><creator>Nitcheu, Josiane</creator><creator>Mahmoudi, Nassira</creator><creator>Ibana, Joyce A</creator><creator>Mangalindan, Gina C</creator><creator>Black, Gregory P</creator><creator>Howard-Jones, Andrew G</creator><creator>Moore, Christopher G</creator><creator>Thomas, Dafydd A</creator><creator>Mazier, Dominique</creator><creator>Ireland, Chris M</creator><creator>Concepcion, Gisela P</creator><creator>Murphy, Patrick J</creator><creator>Diquet, Bertrand</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>M7N</scope></search><sort><creationdate>20060901</creationdate><title>Antimalarial Activity of Crambescidin 800 and Synthetic Analogues against Liver and Blood Stage of Plasmodium sp</title><author>Lazaro, J Enrico H ; Nitcheu, Josiane ; Mahmoudi, Nassira ; Ibana, Joyce A ; Mangalindan, Gina C ; Black, Gregory P ; Howard-Jones, Andrew G ; Moore, Christopher G ; Thomas, Dafydd A ; Mazier, Dominique ; Ireland, Chris M ; Concepcion, Gisela P ; Murphy, Patrick J ; Diquet, Bertrand</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c469t-e5211656cd3820b189af7c471dce0fceaaee6c43d5226358db4f5f2e330967fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Antimalarials - 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toxicity</topic><topic>Survival Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lazaro, J Enrico H</creatorcontrib><creatorcontrib>Nitcheu, Josiane</creatorcontrib><creatorcontrib>Mahmoudi, Nassira</creatorcontrib><creatorcontrib>Ibana, Joyce A</creatorcontrib><creatorcontrib>Mangalindan, Gina C</creatorcontrib><creatorcontrib>Black, Gregory P</creatorcontrib><creatorcontrib>Howard-Jones, Andrew G</creatorcontrib><creatorcontrib>Moore, Christopher G</creatorcontrib><creatorcontrib>Thomas, Dafydd A</creatorcontrib><creatorcontrib>Mazier, Dominique</creatorcontrib><creatorcontrib>Ireland, Chris M</creatorcontrib><creatorcontrib>Concepcion, Gisela P</creatorcontrib><creatorcontrib>Murphy, Patrick J</creatorcontrib><creatorcontrib>Diquet, Bertrand</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Health Medical collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>Journal of antibiotics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lazaro, J Enrico H</au><au>Nitcheu, Josiane</au><au>Mahmoudi, Nassira</au><au>Ibana, Joyce A</au><au>Mangalindan, Gina C</au><au>Black, Gregory P</au><au>Howard-Jones, Andrew G</au><au>Moore, Christopher G</au><au>Thomas, Dafydd A</au><au>Mazier, Dominique</au><au>Ireland, Chris M</au><au>Concepcion, Gisela P</au><au>Murphy, Patrick J</au><au>Diquet, Bertrand</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antimalarial Activity of Crambescidin 800 and Synthetic Analogues against Liver and Blood Stage of Plasmodium sp</atitle><jtitle>Journal of antibiotics</jtitle><stitle>J Antibiot</stitle><addtitle>J Antibiot (Tokyo)</addtitle><date>2006-09-01</date><risdate>2006</risdate><volume>59</volume><issue>9</issue><spage>583</spage><epage>590</epage><pages>583-590</pages><issn>0021-8820</issn><eissn>1881-1469</eissn><abstract>Structural features associated with the antimalarial activity of the marine natural product crambescidin 800 were studied using synthetic analogues of the related compound ptilomycalin A. The study suggests that the guanidine moiety is cytotoxic, whereas the spermidine-containing aliphatic chain increases activity. The most active analogue, compound
11
, had
in vitro
activity against
Plasmodium falciparum
strain 3D7 (IC
50
=490 nM) that was stronger than the
in vitro
activity against murine L5178Y cells (IC
50
=8.5~59 μM).
In vitro
growth inhibition of liver stages of
P. yoelii yoelii
in mouse hepatocytes was observed (IC
50
=9.2 μM). The compound did not significantly prolong median survival time after a single subcutaneous administration of 80 mg/kg in
P. berghei
-infected mice. Compound
11
did not cause DNA fragmentation in an
in vitro
micronucleus assay.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17136890</pmid><doi>10.1038/ja.2006.78</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-8820 |
| ispartof | Journal of antibiotics, 2006-09, Vol.59 (9), p.583-590 |
| issn | 0021-8820 1881-1469 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_19664596 |
| source | MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Animals Antimalarials - chemistry Antimalarials - pharmacology Antimalarials - toxicity Bacteriology Biomedical and Life Sciences Bioorganic Chemistry Cells, Cultured Disease Models, Animal Erythrocytes - parasitology Guanidine - analogs & derivatives Guanidine - chemistry Guanidine - pharmacology Guanidine - toxicity Hepatocytes - parasitology Life Sciences Malaria - drug therapy Medicinal Chemistry Mice Microbiology Molecular Structure Organic Chemistry Parasitic Sensitivity Tests Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium yoelii - drug effects Spiro Compounds - chemistry Spiro Compounds - pharmacology Spiro Compounds - toxicity Survival Analysis |
| title | Antimalarial Activity of Crambescidin 800 and Synthetic Analogues against Liver and Blood Stage of Plasmodium sp |
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