Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds
The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the...
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| Veröffentlicht in: | European journal of medicinal chemistry 2011-11, Vol.46 (11), p.5379-5386 |
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| container_title | European journal of medicinal chemistry |
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| creator | Olmo, Esther del Barboza, Bianca Chiaradia, Louise D. Moreno, Alicia Carrero-Lérida, Juana González-Pacanowska, Dolores Muñoz, Victoria López-Pérez, José L. Giménez, Alberto Benito, Agustín Martínez, Antonio R. Ruiz-Pérez, Luis M. San Feliciano, Arturo |
| description | The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the incorporation of an additional fused ring, were analyzed. Several compounds showed significant antimalarial activity in vitro with IC50 values as low as 60 nM and a certain efficacy in vivo by reducing parasitemia in Plasmodium berghei mouse models.
Benzyl and β-naphthylmethyl derivatives of imidazo[2,1-a]isoindol-5-ol with potent in vitro antiplasmodial effects (IC50 = 60 nM) and promising antimalarial efficacy in vivo (87% inhibition of parasitemia) are described. [Display omitted]
▸ 29 imidazoisoindoles, imidazobenzimidazoles and isoindolinones synthesized. ▸ IC50 values against 3D7 Plasmodium falciparum ranged between 60 nM and >35 mM. ▸ 7 imidazoisoindoles assayed on mice infected with Plasmodium berghei. ▸ Up to 87% parasitemia inhibition on the 5th day, after 4 daily i.p. 25 mg/kg/day. |
| doi_str_mv | 10.1016/j.ejmech.2011.08.043 |
| format | Article |
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Benzyl and β-naphthylmethyl derivatives of imidazo[2,1-a]isoindol-5-ol with potent in vitro antiplasmodial effects (IC50 = 60 nM) and promising antimalarial efficacy in vivo (87% inhibition of parasitemia) are described. [Display omitted]
▸ 29 imidazoisoindoles, imidazobenzimidazoles and isoindolinones synthesized. ▸ IC50 values against 3D7 Plasmodium falciparum ranged between 60 nM and >35 mM. ▸ 7 imidazoisoindoles assayed on mice infected with Plasmodium berghei. ▸ Up to 87% parasitemia inhibition on the 5th day, after 4 daily i.p. 25 mg/kg/day.</description><identifier>ISSN: 0223-5234</identifier><identifier>EISSN: 1768-3254</identifier><identifier>DOI: 10.1016/j.ejmech.2011.08.043</identifier><identifier>PMID: 21940072</identifier><identifier>CODEN: EJMCA5</identifier><language>eng</language><publisher>Kidlington: Elsevier Masson SAS</publisher><subject>Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antimalarials - chemistry ; Antimalarials - pharmacology ; Antimalarials - therapeutic use ; Antimalarials - toxicity ; Antiparasitic agents ; Benzene - chemistry ; Biological and medical sciences ; Cell Line ; Imidazoisoindoles ; Imidazoles - chemistry ; Imidazoles - pharmacology ; Imidazoles - therapeutic use ; Imidazoles - toxicity ; In vitro assays ; In vivo assays ; Inhibitory Concentration 50 ; Isoindoles - chemical synthesis ; Isoindoles - chemistry ; Isoindoles - pharmacology ; Isoindoles - therapeutic use ; Isoindoles - toxicity ; Male ; Medical sciences ; Mice ; Mouse model ; Parasitemia - drug therapy ; Pharmacology. Drug treatments ; Plasmodium berghei ; Plasmodium berghei - drug effects ; Plasmodium berghei - pathogenicity ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Structure–activity relationship ; Synthesis</subject><ispartof>European journal of medicinal chemistry, 2011-11, Vol.46 (11), p.5379-5386</ispartof><rights>2011 Elsevier Masson SAS</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-8e8b6307ada4960bb5f6d62ec6f990a46171e08dc43149107ebb19d9506353573</citedby><cites>FETCH-LOGICAL-c391t-8e8b6307ada4960bb5f6d62ec6f990a46171e08dc43149107ebb19d9506353573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejmech.2011.08.043$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24730028$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21940072$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Olmo, Esther del</creatorcontrib><creatorcontrib>Barboza, Bianca</creatorcontrib><creatorcontrib>Chiaradia, Louise D.</creatorcontrib><creatorcontrib>Moreno, Alicia</creatorcontrib><creatorcontrib>Carrero-Lérida, Juana</creatorcontrib><creatorcontrib>González-Pacanowska, Dolores</creatorcontrib><creatorcontrib>Muñoz, Victoria</creatorcontrib><creatorcontrib>López-Pérez, José L.</creatorcontrib><creatorcontrib>Giménez, Alberto</creatorcontrib><creatorcontrib>Benito, Agustín</creatorcontrib><creatorcontrib>Martínez, Antonio R.</creatorcontrib><creatorcontrib>Ruiz-Pérez, Luis M.</creatorcontrib><creatorcontrib>San Feliciano, Arturo</creatorcontrib><title>Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds</title><title>European journal of medicinal chemistry</title><addtitle>Eur J Med Chem</addtitle><description>The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the incorporation of an additional fused ring, were analyzed. Several compounds showed significant antimalarial activity in vitro with IC50 values as low as 60 nM and a certain efficacy in vivo by reducing parasitemia in Plasmodium berghei mouse models.
Benzyl and β-naphthylmethyl derivatives of imidazo[2,1-a]isoindol-5-ol with potent in vitro antiplasmodial effects (IC50 = 60 nM) and promising antimalarial efficacy in vivo (87% inhibition of parasitemia) are described. [Display omitted]
▸ 29 imidazoisoindoles, imidazobenzimidazoles and isoindolinones synthesized. ▸ IC50 values against 3D7 Plasmodium falciparum ranged between 60 nM and >35 mM. ▸ 7 imidazoisoindoles assayed on mice infected with Plasmodium berghei. ▸ Up to 87% parasitemia inhibition on the 5th day, after 4 daily i.p. 25 mg/kg/day.</description><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antimalarials - chemistry</subject><subject>Antimalarials - pharmacology</subject><subject>Antimalarials - therapeutic use</subject><subject>Antimalarials - toxicity</subject><subject>Antiparasitic agents</subject><subject>Benzene - chemistry</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Imidazoisoindoles</subject><subject>Imidazoles - chemistry</subject><subject>Imidazoles - pharmacology</subject><subject>Imidazoles - therapeutic use</subject><subject>Imidazoles - toxicity</subject><subject>In vitro assays</subject><subject>In vivo assays</subject><subject>Inhibitory Concentration 50</subject><subject>Isoindoles - chemical synthesis</subject><subject>Isoindoles - chemistry</subject><subject>Isoindoles - pharmacology</subject><subject>Isoindoles - therapeutic use</subject><subject>Isoindoles - toxicity</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mouse model</subject><subject>Parasitemia - drug therapy</subject><subject>Pharmacology. Drug treatments</subject><subject>Plasmodium berghei</subject><subject>Plasmodium berghei - drug effects</subject><subject>Plasmodium berghei - pathogenicity</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Structure–activity relationship</subject><subject>Synthesis</subject><issn>0223-5234</issn><issn>1768-3254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2LFDEQhoMo7uzqPxDpi-xlu618dLpzEZbFL1jwol5EQnVSjRnSnTHpGVh_vT3MqDdPdXneeqsexl5waDhw_Xrb0HYi96MRwHkDfQNKPmIb3um-lqJVj9kGhJB1K6S6YJelbAGg1QBP2YXgRgF0YsO-3s5LmDBiDhgrdEs4hOWhSmMVpuDxV_ombniN30NJYfYp1m2dYuUphwOuLJUKZ19liriQr1yadmk_-_KMPRkxFnp-nlfsy7u3n-8-1Pef3n-8u72vnTR8qXvqBy2hQ4_KaBiGdtReC3J6NAZQad5xgt47JbkyHDoaBm68aUHLVradvGLXp727nH7uqSx2CsVRjDhT2hdrYCWVUP1KqhPpciol02h3eX08P1gO9ijUbu1JqD0KtdDbVegae3ku2A8T-b-hPwZX4NUZwOIwjhlnF8o_TnUSQBz735w4WnUcAmVbXKDZkQ-Z3GJ9Cv-_5DeWDJS3</recordid><startdate>20111101</startdate><enddate>20111101</enddate><creator>Olmo, Esther del</creator><creator>Barboza, Bianca</creator><creator>Chiaradia, Louise D.</creator><creator>Moreno, Alicia</creator><creator>Carrero-Lérida, Juana</creator><creator>González-Pacanowska, Dolores</creator><creator>Muñoz, Victoria</creator><creator>López-Pérez, José L.</creator><creator>Giménez, Alberto</creator><creator>Benito, Agustín</creator><creator>Martínez, Antonio R.</creator><creator>Ruiz-Pérez, Luis M.</creator><creator>San Feliciano, Arturo</creator><general>Elsevier Masson SAS</general><general>Elsevier</general><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><scope>7X8</scope></search><sort><creationdate>20111101</creationdate><title>Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds</title><author>Olmo, Esther del ; Barboza, Bianca ; Chiaradia, Louise D. ; Moreno, Alicia ; Carrero-Lérida, Juana ; González-Pacanowska, Dolores ; Muñoz, Victoria ; López-Pérez, José L. ; Giménez, Alberto ; Benito, Agustín ; Martínez, Antonio R. ; Ruiz-Pérez, Luis M. ; San Feliciano, Arturo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-8e8b6307ada4960bb5f6d62ec6f990a46171e08dc43149107ebb19d9506353573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antimalarials - chemistry</topic><topic>Antimalarials - pharmacology</topic><topic>Antimalarials - therapeutic use</topic><topic>Antimalarials - toxicity</topic><topic>Antiparasitic agents</topic><topic>Benzene - chemistry</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Imidazoisoindoles</topic><topic>Imidazoles - chemistry</topic><topic>Imidazoles - pharmacology</topic><topic>Imidazoles - therapeutic use</topic><topic>Imidazoles - toxicity</topic><topic>In vitro assays</topic><topic>In vivo assays</topic><topic>Inhibitory Concentration 50</topic><topic>Isoindoles - chemical synthesis</topic><topic>Isoindoles - chemistry</topic><topic>Isoindoles - pharmacology</topic><topic>Isoindoles - therapeutic use</topic><topic>Isoindoles - toxicity</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mouse model</topic><topic>Parasitemia - drug therapy</topic><topic>Pharmacology. Drug treatments</topic><topic>Plasmodium berghei</topic><topic>Plasmodium berghei - drug effects</topic><topic>Plasmodium berghei - pathogenicity</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Structure–activity relationship</topic><topic>Synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Olmo, Esther del</creatorcontrib><creatorcontrib>Barboza, Bianca</creatorcontrib><creatorcontrib>Chiaradia, Louise D.</creatorcontrib><creatorcontrib>Moreno, Alicia</creatorcontrib><creatorcontrib>Carrero-Lérida, Juana</creatorcontrib><creatorcontrib>González-Pacanowska, Dolores</creatorcontrib><creatorcontrib>Muñoz, Victoria</creatorcontrib><creatorcontrib>López-Pérez, José L.</creatorcontrib><creatorcontrib>Giménez, Alberto</creatorcontrib><creatorcontrib>Benito, Agustín</creatorcontrib><creatorcontrib>Martínez, Antonio R.</creatorcontrib><creatorcontrib>Ruiz-Pérez, Luis M.</creatorcontrib><creatorcontrib>San Feliciano, Arturo</creatorcontrib><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><collection>MEDLINE - Academic</collection><jtitle>European journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Olmo, Esther del</au><au>Barboza, Bianca</au><au>Chiaradia, Louise D.</au><au>Moreno, Alicia</au><au>Carrero-Lérida, Juana</au><au>González-Pacanowska, Dolores</au><au>Muñoz, Victoria</au><au>López-Pérez, José L.</au><au>Giménez, Alberto</au><au>Benito, Agustín</au><au>Martínez, Antonio R.</au><au>Ruiz-Pérez, Luis M.</au><au>San Feliciano, Arturo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds</atitle><jtitle>European journal of medicinal chemistry</jtitle><addtitle>Eur J Med Chem</addtitle><date>2011-11-01</date><risdate>2011</risdate><volume>46</volume><issue>11</issue><spage>5379</spage><epage>5386</epage><pages>5379-5386</pages><issn>0223-5234</issn><eissn>1768-3254</eissn><coden>EJMCA5</coden><abstract>The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the incorporation of an additional fused ring, were analyzed. Several compounds showed significant antimalarial activity in vitro with IC50 values as low as 60 nM and a certain efficacy in vivo by reducing parasitemia in Plasmodium berghei mouse models.
Benzyl and β-naphthylmethyl derivatives of imidazo[2,1-a]isoindol-5-ol with potent in vitro antiplasmodial effects (IC50 = 60 nM) and promising antimalarial efficacy in vivo (87% inhibition of parasitemia) are described. [Display omitted]
▸ 29 imidazoisoindoles, imidazobenzimidazoles and isoindolinones synthesized. ▸ IC50 values against 3D7 Plasmodium falciparum ranged between 60 nM and >35 mM. ▸ 7 imidazoisoindoles assayed on mice infected with Plasmodium berghei. ▸ Up to 87% parasitemia inhibition on the 5th day, after 4 daily i.p. 25 mg/kg/day.</abstract><cop>Kidlington</cop><pub>Elsevier Masson SAS</pub><pmid>21940072</pmid><doi>10.1016/j.ejmech.2011.08.043</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antimalarials - chemistry Antimalarials - pharmacology Antimalarials - therapeutic use Antimalarials - toxicity Antiparasitic agents Benzene - chemistry Biological and medical sciences Cell Line Imidazoisoindoles Imidazoles - chemistry Imidazoles - pharmacology Imidazoles - therapeutic use Imidazoles - toxicity In vitro assays In vivo assays Inhibitory Concentration 50 Isoindoles - chemical synthesis Isoindoles - chemistry Isoindoles - pharmacology Isoindoles - therapeutic use Isoindoles - toxicity Male Medical sciences Mice Mouse model Parasitemia - drug therapy Pharmacology. Drug treatments Plasmodium berghei Plasmodium berghei - drug effects Plasmodium berghei - pathogenicity Plasmodium falciparum Plasmodium falciparum - drug effects Structure–activity relationship Synthesis |
| title | Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds |
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