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dc.contributor.authorValente, Mariaes_ES
dc.contributor.authorVidal, Antonio E.es_ES
dc.contributor.authorGonzález-Pacanowska, D.es_ES
dc.date.accessioned2019-12-02T09:54:10Z-
dc.date.available2019-12-02T09:54:10Z-
dc.date.issued2019-
dc.identifier.citationCurrent Medicinal Chemistryes_ES
dc.identifier.issn0929-8673-
dc.identifier.urihttp://hdl.handle.net/10261/195806-
dc.description.abstractKinetoplastid and apicomplexan parasites comprise a group of protozoans responsible for human diseases, with a serious impact on human health and the socioeconomic growth of developing countries. Chemotherapy is the main option to control these pathogenic organisms and nucleotide metabolism is considered a promising area for the provision of antimicrobial therapeutic targets. Impairment of thymidylate (dTMP) biosynthesis severely diminishes the viability of parasitic protozoa and the absence of enzymatic activities specifically involved in the formation of dTMP (e.g. dUTPase, thymidylate synthase, dihydrofolate reductase or thymidine kinase) results in decreased deoxythymidine triphosphate (dTTP) levels and the so-called thymineless death. In this process, the ratio of deoxyuridine triphosphate (dUTP) versus dTTP in the cellular nucleotide pool has a crucial role. A high dUTP/dTTP ratio leads to uracil misincorporation into DNA, the activation of DNA repair pathways, DNA fragmentation and eventually cell death. The essential character of dTMP synthesis has stimulated interest in the identification and development of drugs that specifically block the biochemical steps involved in thymine nucleotide formation. Here, we review the available literature in relation to drug discovery studies targeting thymidylate biosynthesis in kinetoplastid (genera Trypanosoma and Leishmania) and apicomplexan (Plasmodium spp and Toxoplasma gondii) protozoans. The most relevant findings concerning novel inhibitory molecules with antiparasitic activity against these human pathogens are presented herein.es_ES
dc.description.sponsorshipThis work was supported by the Junta de Andalucia [BIO-199], the Plan Nacional de Investigacion Cientifica, Instituto de Salud Carlos III-Subdireccion General de Redes y Centros de Investigacion Cooperativa-Red de Investigacion Cooperativa en Enfermedades Tropicales (RICET FIS Network: RD12/0018/0017), the Plan Nacional (SAF2016-79957-R) and the FEDER funds from the EU.es_ES
dc.language.isoenges_ES
dc.publisherBentham Science Publisherses_ES
dc.relationMINECO/ICTI2013-2016/SAF2016-79957-Res_ES
dc.rightsclosedAccesses_ES
dc.subjectThymidylate biosynthesises_ES
dc.subjectkinetoplastidaes_ES
dc.subjectapicomplexaes_ES
dc.subjectdrug targetes_ES
dc.subjectinhibitores_ES
dc.subjectpyrimidinees_ES
dc.subjectdTMPes_ES
dc.subjectanti protozoales_ES
dc.titleTargeting Kinetoplastid and Apicomplexan Thymidylate Biosynthesis as an Antiprotozoal Strategyes_ES
dc.typerevisiónes_ES
dc.identifier.doihttp://dx.doi.org/10.2174/0929867325666180926154329-
dc.description.peerreviewedPeer reviewedes_ES
dc.identifier.e-issn1875-533X-
dc.contributor.funderMinisterio de Economía y Empresa (España)es_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.contributor.funderJunta de Andalucíaes_ES
dc.contributor.funderEuropean Commissiones_ES
dc.contributor.funderRed de Investigación Cooperativa en Enfermedades Tropicales (España)es_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100011011es_ES
dc.identifier.pmid30259810-
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