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http://hdl.handle.net/10261/279866
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dc.contributor.author | Fonseca-Berzal, Cristina | es_ES |
dc.contributor.author | Ibáñez-Escribano, Alexandra | es_ES |
dc.contributor.author | Castro, Sonia de | es_ES |
dc.contributor.author | Escario, José A. | es_ES |
dc.contributor.author | Gómez-Barrio, Alicia | es_ES |
dc.contributor.author | Arán, Vicente J. | es_ES |
dc.date.accessioned | 2022-09-26T11:30:23Z | - |
dc.date.available | 2022-09-26T11:30:23Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | Acta Tropica 234 : 106607 (2022) | es_ES |
dc.identifier.uri | http://hdl.handle.net/10261/279866 | - |
dc.description.abstract | In this study, a new series of eleven 5-nitroindazole derivatives (10−20) and a related 6-nitroquinazoline (21) was synthesized and tested in vitro against different forms of the kinetoplastid parasite Trypanosoma cruzi, etiological agent of Chagas disease. Among these compounds, derivatives 11−14 and 17 showed trypanocidal profiles on epimastigotes (IC50 = 1.00−8.75 µM) considerably better than that of the reference drug benznidazole, BZ (IC50 = 25.22 µM). Furthermore, the lack of cytotoxicity observed for compounds 11, 12, 14, 17 and 18 over L929 fibroblasts, led to a notable selectivity (SI) on the extracellular replicative form of the parasite: SIEPI > 12.41 to > 256 µM. Since these five derivatives overpassed the cut-off value established by BZ (SIEPI ≥ 10), they were moved to a more specific assay against the intracellular and replicative form of T. cruzi, i.e, amastigotes. These molecules were not as active as BZ (IC50 = 0.57 µM) against this parasite form; however, all of them showed remarkable IC50 values lower than 7 µM. Special mention deserve compounds 12 and 17, whose SIAMA were > 246.15 and > 188.23, respectively. The results compiled in the present work, point to a positive impact over the trypanocidal activity of the electron withdrawing substituents introduced at position 2 of the N-2 benzyl moiety of these compounds, especially fluorine, i.e., derivatives 12 and 17. These outcomes, supported by the in silico prediction of good oral bioavailability and suitable risk profile, reinforce the 5-nitroindazole scaffold as an adequate template for preparing potential antichagasic agents. | es_ES |
dc.description.sponsorship | This work was partially supported by the Spanish Ministry of Econ- omy, Industry and Competitiveness (MINEICO, ref. SAF2015-66690-R) and the 911120 UCM Research Group “Epidemiología, Diagnóstico y Terapia Antiparasitaria”. The Spanish Ministry of Science, Innovation and Universities (MICIU, ref. RTI2018-093940-B-I00) is also acknowledged | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.relation | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-093940-B-I00/ES/DESARROLLO DE FARMACOS DIRIGIDOS A LA MITOCONDRIA Y ORGANULOS SIMILARES COMO ENFOQUE TERAPEUTICO PARA EL TRATAMIENTO DE ENFERMEDADES PARASITARIAS DESATENDIDAS/ | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO//SAF2015-66690-R/ES/APROXIMACIONES BASADAS EN LA DIANA Y FENOTIPICAS PARA EL DESCUBRIMIENTO DE NUEVOS FARMACOS CONTRA LAS TRIPANOSOMIASIS AFRICANA Y AMERICANA/ | es_ES |
dc.rights | closedAccess | es_ES |
dc.subject | Chagas disease | es_ES |
dc.subject | Indazole | es_ES |
dc.subject | Nitroheterocycle | es_ES |
dc.subject | In silico | es_ES |
dc.subject | In vitro | es_ES |
dc.title | 5-Nitroindazole-based compounds: further studies for activity optimization as anti-Trypanosoma cruzi agents | es_ES |
dc.type | artículo | es_ES |
dc.identifier.doi | 10.1016/j.jand.2021.04.020 | - |
dc.description.peerreviewed | Peer reviewed | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.actatropica.2022.106607 | es_ES |
dc.contributor.funder | Ministerio de Economía, Industria y Competitividad (España) | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.relation.csic | Sí | es_ES |
oprm.item.hasRevision | no ko 0 false | * |
dc.identifier.funder | http://dx.doi.org/10.13039/501100010198 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004837 | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.languageiso639-1 | en | - |
item.fulltext | No Fulltext | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
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