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dc.contributor | Facultad de Veterinaria | es_ES |
dc.contributor.author | Pérez Pertejo, Maria Yolanda | |
dc.contributor.author | Escudero Martínez, José Miguel | |
dc.contributor.author | Reguera Torres, Rosa María | |
dc.contributor.author | Balaña Fouce, Rafael | |
dc.contributor.author | García, Pablo A. | |
dc.contributor.author | Jambrina, Pablo G. | |
dc.contributor.author | San Feliciano Martín, Arturo | |
dc.contributor.other | Toxicologia | es_ES |
dc.date | 2019-10-22 | |
dc.date.accessioned | 2024-01-25T13:03:25Z | |
dc.date.available | 2024-01-25T13:03:25Z | |
dc.identifier.citation | Pérez-Pertejo, Y., Escudero-Martínez, J. M., Reguera, R. M., Balaña-Fouce, R., García, P. A., Jambrina, P. G., San Feliciano, A., & Castro, M.-Á. (2019). Antileishmanial activity of terpenylquinones on Leishmania infantum and their effects on Leishmania topoisomerase IB. International Journal for Parasitology: Drugs and Drug Resistance, 11, 70-79. https://doi.org/10.1016/J.IJPDDR.2019.10.004 | es_ES |
dc.identifier.issn | 2211-3207 | |
dc.identifier.other | https://www.sciencedirect.com/science/article/pii/S2211320719301095?via%3Dihub | es_ES |
dc.identifier.uri | https://hdl.handle.net/10612/17813 | |
dc.description.abstract | [EN] Leishmania is the aethiological agent responsible for the visceral leishmaniasis, a serious parasite-borne disease widely spread all over the World. The emergence of resistant strains makes classical treatments less effective; therefore, new and better drugs are necessary. Naphthoquinones are interesting compounds for which many pharmacological properties have been described, including leishmanicidal activity. This work shows the antileishmanial effect of two series of terpenyl-1,4-naphthoquinones (NQ) and 1,4-anthraquinones (AQ) obtained from natural terpenoids, such as myrcene and myrceocommunic acid. They were evaluated both in vitro and ex vivo against the transgenic iRFP-Leishmania infantum strain and also tested on liver HepG2 cells to determine their selectivity indexes. The results indicated that NQ derivatives showed better antileishmanial activity than AQ analogues, and among them, compounds with a diacetylated hydroquinone moiety provided better results than their corresponding quinones. Regarding the terpenic precursor, compounds obtained from the monoterpenoid myrcene displayed good antiparasitic efficiency and low cytotoxicity for mammalian cells, whereas those derived from the diterpenoid showed better antileishmanial activity without selectivity. In order to explore their mechanism of action, all the compounds have been tested as potential inhibitors of Leishmania type IB DNA topoisomerases, but only some compounds that displayed the quinone ring were able to inhibit the recombinant enzyme in vitro. This fact together with the docking studies performed on LTopIB suggested the existence of another mechanism of action, alternative or complementary to LTopIB inhibition. In silico druglikeness and ADME evaluation of the best leishmanicidal compounds has shown good predictable druggability | es_ES |
dc.language | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Farmacología | es_ES |
dc.subject | Medicina. Salud | es_ES |
dc.subject.other | Leishmania infantum | es_ES |
dc.subject.other | Terpenylquinones | es_ES |
dc.subject.other | Naphthoquinones | es_ES |
dc.subject.other | Anthraquinones | es_ES |
dc.subject.other | Acridinequinone | es_ES |
dc.subject.other | DNA-Topoisomerase IB | es_ES |
dc.title | Antileishmanial activity of terpenylquinones on Leishmania infantum and their effects on Leishmania topoisomerase IB | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.identifier.doi | 10.1016/j.ijpddr.2019.10.004 | |
dc.description.peerreviewed | SI | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/MINECO/Programa Estatal de I+D+I Orientada a los Retos de la Sociedad/CTQ2015-68175-R/ES/NUEVAS ESTRATEGIAS DE SINTESIS Y FUNCIONALIZACION DE ANALGESICOS Y CITOTOXICOS// | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/AEI/Programa Estatal de I+D+i Orientada a los Retos de la Sociedad /SAF2017-83575-R/ES/AUTOVIA A LOS LISOSOMAS: DIRIGIENDO A MACROFAGOS INFECTADOS// | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.journal.title | International Journal for Parasitology: Drugs and Drug Resistance | es_ES |
dc.volume.number | 11 | es_ES |
dc.page.initial | 70 | es_ES |
dc.page.final | 79 | es_ES |
dc.type.hasVersion | info:eu-repo/semantics/publishedVersion | es_ES |
dc.subject.unesco | 3109 Ciencias Veterinarias | es_ES |
dc.subject.unesco | 3214 Toxicología | es_ES |
dc.description.project | Financial support came from Spanish MINECO (CTQ2015-68175-R, AGL2016-79813-C2-1-R, AGL2016-79813-C2-2-R and SAF2017-83575-R), ISCIII-RICET Network (RD12/0018/0002) and Consejería de Educación de la Junta de Castilla y León (LE020P17) co-financed by the Fondo Social Europeo of the European Union (FEDER-EU). P. G. J. acknowledges funding by Fundación Salamanca Ciudad de Cultura y Saberes (’‘Programme for attracting scientific talent to Salamanca’‘) | es_ES |
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