Antimalarial drugs – host targets (re)visited
Identifieur interne : 000796 ( Istex/Corpus ); précédent : 000795; suivant : 000797Antimalarial drugs – host targets (re)visited
Auteurs : Margarida Cunha-Rodrigues ; Miguel Prudêncio ; Maria M. Mota ; Werner HaasSource :
- Biotechnology Journal [ 1860-6768 ] ; 2006-03.
Abstract
Every year, forty percent of the world population is at risk of contracting malaria. Hopes for the erradication of this disease during the 20th century were dashed by the ability of Plasmodium falciparum, its most deadly causative agent, to develop resistance to available drugs. Efforts to produce an effective vaccine have so far been unsuccessful, enhancing the need to develop novel antimalarial drugs. In this review, we summarize our knowledge concerning existing antimalarials, mechanisms of drug‐resistance development, the use of drug combination strategies and the quest for novel anti‐plasmodial compounds. We emphasize the potential role of host genes and molecules as novel targets for newly developed drugs. Recent results from our laboratory have shown Hepatocyte Growth Factor/MET signaling to be essential for the establishment of infection in hepatocytes. We discuss the potential use of this pathway in the prophylaxis of malaria infection.
Url:
DOI: 10.1002/biot.200500038
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ISTEX:E9EAFDD2B3575B9E156BAE0F1E7645BBC6CB79E5Le document en format XML
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KGaA, Weinheim</copyright><eventGroup><event type="manuscriptReceived" date="2005-11-25"></event><event type="manuscriptRevised" date="2005-12-08"></event><event type="manuscriptAccepted" date="2006-01-12"></event><event type="firstOnline" date="2006-02-22"></event><event type="publishedOnlineFinalForm" date="2006-03-17"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.2 mode:FullText source:HeaderRef result:HeaderRef" date="2010-03-05"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-07"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-15"></event></eventGroup><numberingGroup><numbering type="pageFirst">321</numbering><numbering type="pageLast">332</numbering></numberingGroup><correspondenceTo>Unidade de Malária, Instituto de Medicina Molecular,Universidade de Lisboa, 1649‐028 Lisboa, Portugal, <b>Fax:</b> +351 21 799 95 04</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:BIOT.BIOT321.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="1"></count><count type="referenceTotal" number="229"></count></countGroup><titleGroup><title type="main" xml:lang="en">Antimalarial drugs – host targets (re)visited</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#a1"><personName><givenNames>Margarida</givenNames><familyName>Cunha‐Rodrigues</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#a1"><personName><givenNames>Miguel</givenNames><familyName>Prudêncio</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#a1" corresponding="yes"><personName><givenNames>Maria M.</givenNames><familyName>Mota</familyName><degrees>Dr.</degrees></personName><contactDetails><email>mmota@fm.ul.pt</email></contactDetails></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#a2"><personName><givenNames>Werner</givenNames><familyName>Haas</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="PT" type="organization"><unparsedAffiliation>Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="PT" type="organization"><unparsedAffiliation>Alfama, Taguspark, Porto Salvo, Portugal</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Malaria</keyword><keyword xml:id="kwd2">Prophylaxis</keyword><keyword xml:id="kwd3">Drug resistance</keyword><keyword xml:id="kwd4">HGF/MET</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Every year, forty percent of the world population is at risk of contracting malaria. Hopes for the erradication of this disease during the 20th century were dashed by the ability of <i>Plasmodium falciparum</i>, its most deadly causative agent, to develop resistance to available drugs. Efforts to produce an effective vaccine have so far been unsuccessful, enhancing the need to develop novel antimalarial drugs. In this review, we summarize our knowledge concerning existing antimalarials, mechanisms of drug‐resistance development, the use of drug combination strategies and the quest for novel anti‐plasmodial compounds. We emphasize the potential role of host genes and molecules as novel targets for newly developed drugs. Recent results from our laboratory have shown Hepatocyte Growth Factor/MET signaling to be essential for the establishment of infection in hepatocytes. We discuss the potential use of this pathway in the prophylaxis of malaria infection.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Antimalarial drugs – host targets (re)visited</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Antimalarial drugs – host targets (re)visited</title></titleInfo><name type="personal"><namePart type="given">Margarida</namePart><namePart type="family">Cunha‐Rodrigues</namePart><affiliation>Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Miguel</namePart><namePart type="family">Prudêncio</namePart><affiliation>Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maria M.</namePart><namePart type="family">Mota</namePart><namePart type="termsOfAddress">Dr.</namePart><affiliation>Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal</affiliation><affiliation>E-mail: mmota@fm.ul.pt</affiliation><affiliation>Correspondence address: Unidade de Malária, Instituto de Medicina Molecular,Universidade de Lisboa, 1649‐028 Lisboa, Portugal, +351 21 799 95 04</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Werner</namePart><namePart type="family">Haas</namePart><affiliation>Alfama, Taguspark, Porto Salvo, Portugal</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>WILEY‐VCH Verlag</publisher><place><placeTerm type="text">Weinheim</placeTerm></place><dateIssued encoding="w3cdtf">2006-03</dateIssued><dateCaptured encoding="w3cdtf">2005-11-25</dateCaptured><dateValid encoding="w3cdtf">2006-01-12</dateValid><copyrightDate encoding="w3cdtf">2006</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">0</extent><extent unit="tables">1</extent><extent unit="references">229</extent></physicalDescription><abstract lang="en">Every year, forty percent of the world population is at risk of contracting malaria. Hopes for the erradication of this disease during the 20th century were dashed by the ability of Plasmodium falciparum, its most deadly causative agent, to develop resistance to available drugs. Efforts to produce an effective vaccine have so far been unsuccessful, enhancing the need to develop novel antimalarial drugs. In this review, we summarize our knowledge concerning existing antimalarials, mechanisms of drug‐resistance development, the use of drug combination strategies and the quest for novel anti‐plasmodial compounds. We emphasize the potential role of host genes and molecules as novel targets for newly developed drugs. Recent results from our laboratory have shown Hepatocyte Growth Factor/MET signaling to be essential for the establishment of infection in hepatocytes. 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