Chloroquine–astemizole hybrids with potent in vitro and in vivo antiplasmodial activity
A series of novel hybrids of CQ and astemizole have been shown to possess potent in vitro and in vivo antiplasmodial activity. A dual activity, conjugated approach has been taken to form hybrid molecules of two known antimalarial drugs, chloroquine (CQ) and the non-sedating H1 antagonist astemizole....
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2009-01, Vol.19 (2), p.481-484 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Musonda, Chitalu C. Whitlock, Gavin A. Witty, Michael J. Brun, Reto Kaiser, Marcel |
| description | A series of novel hybrids of CQ and astemizole have been shown to possess potent in vitro and in vivo antiplasmodial activity.
A dual activity, conjugated approach has been taken to form hybrid molecules of two known antimalarial drugs, chloroquine (CQ) and the non-sedating H1 antagonist astemizole. A variety of linkers were investigated to conjugate the two agents into one molecule. Compounds
5–
8 possessed improved in vitro activity against a CQ-resistant strain of
Plasmodium falciparum, and examples
7 and
8 were active in vivo in mouse models of malaria. |
| doi_str_mv | 10.1016/j.bmcl.2008.11.047 |
| format | Article |
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A dual activity, conjugated approach has been taken to form hybrid molecules of two known antimalarial drugs, chloroquine (CQ) and the non-sedating H1 antagonist astemizole. A variety of linkers were investigated to conjugate the two agents into one molecule. Compounds
5–
8 possessed improved in vitro activity against a CQ-resistant strain of
Plasmodium falciparum, and examples
7 and
8 were active in vivo in mouse models of malaria.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2008.11.047</identifier><identifier>PMID: 19054674</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antimalarials - chemistry ; Antimalarials - pharmacology ; Antimalarials - therapeutic use ; Antiparasitic agents ; Astemizole - chemistry ; Astemizole - pharmacology ; Astemizole - therapeutic use ; Biological and medical sciences ; Chloroquine - chemistry ; Chloroquine - pharmacology ; Chloroquine - therapeutic use ; Conjugated approach ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Hybrid ; Malaria ; Malaria, Falciparum - drug therapy ; Medical sciences ; Mice ; Pharmacology. Drug treatments ; Plasmodium falciparum ; Plasmodium falciparum - drug effects</subject><ispartof>Bioorganic & medicinal chemistry letters, 2009-01, Vol.19 (2), p.481-484</ispartof><rights>2008 Elsevier Ltd</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-8777582b483f82b55f9bb71fa616748c6a2f972c65b67e4a5d94cb40b43a8edb3</citedby><cites>FETCH-LOGICAL-c415t-8777582b483f82b55f9bb71fa616748c6a2f972c65b67e4a5d94cb40b43a8edb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2008.11.047$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21030495$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19054674$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Musonda, Chitalu C.</creatorcontrib><creatorcontrib>Whitlock, Gavin A.</creatorcontrib><creatorcontrib>Witty, Michael J.</creatorcontrib><creatorcontrib>Brun, Reto</creatorcontrib><creatorcontrib>Kaiser, Marcel</creatorcontrib><title>Chloroquine–astemizole hybrids with potent in vitro and in vivo antiplasmodial activity</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A series of novel hybrids of CQ and astemizole have been shown to possess potent in vitro and in vivo antiplasmodial activity.
A dual activity, conjugated approach has been taken to form hybrid molecules of two known antimalarial drugs, chloroquine (CQ) and the non-sedating H1 antagonist astemizole. A variety of linkers were investigated to conjugate the two agents into one molecule. Compounds
5–
8 possessed improved in vitro activity against a CQ-resistant strain of
Plasmodium falciparum, and examples
7 and
8 were active in vivo in mouse models of malaria.</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>Antiparasitic agents</subject><subject>Astemizole - chemistry</subject><subject>Astemizole - pharmacology</subject><subject>Astemizole - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Chloroquine - chemistry</subject><subject>Chloroquine - pharmacology</subject><subject>Chloroquine - therapeutic use</subject><subject>Conjugated approach</subject><subject>Disease Models, Animal</subject><subject>Drug Evaluation, Preclinical</subject><subject>Hybrid</subject><subject>Malaria</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Pharmacology. 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Antiinfectious agents. Antiparasitic agents</topic><topic>Antimalarials - chemistry</topic><topic>Antimalarials - pharmacology</topic><topic>Antimalarials - therapeutic use</topic><topic>Antiparasitic agents</topic><topic>Astemizole - chemistry</topic><topic>Astemizole - pharmacology</topic><topic>Astemizole - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Chloroquine - chemistry</topic><topic>Chloroquine - pharmacology</topic><topic>Chloroquine - therapeutic use</topic><topic>Conjugated approach</topic><topic>Disease Models, Animal</topic><topic>Drug Evaluation, Preclinical</topic><topic>Hybrid</topic><topic>Malaria</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Pharmacology. 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A dual activity, conjugated approach has been taken to form hybrid molecules of two known antimalarial drugs, chloroquine (CQ) and the non-sedating H1 antagonist astemizole. A variety of linkers were investigated to conjugate the two agents into one molecule. Compounds
5–
8 possessed improved in vitro activity against a CQ-resistant strain of
Plasmodium falciparum, and examples
7 and
8 were active in vivo in mouse models of malaria.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>19054674</pmid><doi>10.1016/j.bmcl.2008.11.047</doi><tpages>4</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2009-01, Vol.19 (2), p.481-484 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antimalarials - chemistry Antimalarials - pharmacology Antimalarials - therapeutic use Antiparasitic agents Astemizole - chemistry Astemizole - pharmacology Astemizole - therapeutic use Biological and medical sciences Chloroquine - chemistry Chloroquine - pharmacology Chloroquine - therapeutic use Conjugated approach Disease Models, Animal Drug Evaluation, Preclinical Hybrid Malaria Malaria, Falciparum - drug therapy Medical sciences Mice Pharmacology. Drug treatments Plasmodium falciparum Plasmodium falciparum - drug effects |
| title | Chloroquine–astemizole hybrids with potent in vitro and in vivo antiplasmodial activity |
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