Mostrar el registro sencillo del ítem
dc.contributor.author
Soba, Mariano
dc.contributor.author
Scalese, Gonzalo
dc.contributor.author
Casuriaga, Federico
dc.contributor.author
Pérez, Nicolás
dc.contributor.author
Veiga, Nicolás
dc.contributor.author
Echeverría, Gustavo Alberto
dc.contributor.author
Piro, Oscar Enrique
dc.contributor.author
Faccio, Ricardo
dc.contributor.author
Pérez Díaz, Leticia
dc.contributor.author
Gasser, Gilles
dc.contributor.author
Machado, Ignacio
dc.contributor.author
Gambino, Dinorah
dc.date.available
2024-08-20T14:46:40Z
dc.date.issued
2023-01
dc.identifier.citation
Soba, Mariano; Scalese, Gonzalo; Casuriaga, Federico; Pérez, Nicolás; Veiga, Nicolás; et al.; Multifunctional organometallic compounds for the treatment of Chagas disease: Re(i) tricarbonyl compounds with two different bioactive ligands; Royal Society of Chemistry; Dalton Transactions; 52; 6; 1-2023; 1623-1641
dc.identifier.issn
1477-9226
dc.identifier.uri
http://hdl.handle.net/11336/242878
dc.description.abstract
Chagas' disease (American Trypanosomiasis) is an ancient and endemic illness in Latin America caused by the protozoan parasite Trypanosoma cruzi. Although there is an urgent need for more efficient and less toxic chemotherapeutics, no new drugs to treat this disease have entered the clinic in the last decades. Searching for metal-based prospective antichagasic drugs, in this work, multifunctional Re(i) tricarbonyl compounds bearing two different bioactive ligands were designed: a polypyridyl NN derivative of 1,10-phenanthroline and a monodentate azole (Clotrimazole CTZ or Ketoconazol KTZ). Five fac-[Re(CO)3(NN)(CTZ)](PF6) compounds and a fac-[Re(CO)3(NN)(KTZ)](PF6) were synthesized and fully characterized. They showed activity against epimastigotes (IC50 3.48-9.42 μM) and trypomastigotes of T. cruzi (IC50 0.61-2.79 μM) and moderate to good selectivity towards the parasite compared to the VERO mammalian cell model. In order to unravel the mechanism of action of our compounds, two potential targets were experimentally and theoretically studied, namely DNA and one of the enzymes involved in the parasite ergosterol biosynthetic pathway, CYP51 (lanosterol 14-α-demethylase). As hypothesized, the multifunctional compounds shared in vitro a similar mode of action as that disclosed for the single bioactive moieties included in the new chemical entities. Additionally, two relevant physicochemical properties of biological interest in prospective drug development, namely lipophilicity and stability in solution in different media, were determined. The whole set of results demonstrates the potentiality of these Re(i) tricarbonyls as promising candidates for further antitrypanosomal drug development.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Royal Society of Chemistry
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
STRUCTURAL X-RAY DIFFRACTION
dc.subject
Chagas disease
dc.subject
Clotrimazole
dc.subject
Metals in medicine
dc.subject
Multifunctional metal compounds
dc.subject
Re(I) complexes
dc.subject
Trypanosoma cruzi
dc.subject.classification
Física Atómica, Molecular y Química
dc.subject.classification
Ciencias Físicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.subject.classification
Físico-Química, Ciencia de los Polímeros, Electroquímica
dc.subject.classification
Ciencias Químicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.subject.classification
Otras Ciencias Químicas
dc.subject.classification
Ciencias Químicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Multifunctional organometallic compounds for the treatment of Chagas disease: Re(i) tricarbonyl compounds with two different bioactive ligands
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-04-17T12:23:14Z
dc.journal.volume
52
dc.journal.number
6
dc.journal.pagination
1623-1641
dc.journal.pais
Reino Unido
dc.description.fil
Fil: Soba, Mariano. Universidad de la República; Uruguay
dc.description.fil
Fil: Scalese, Gonzalo. Universidad de la República; Uruguay
dc.description.fil
Fil: Casuriaga, Federico. Universidad de la República; Uruguay
dc.description.fil
Fil: Pérez, Nicolás. Universidad de la República; Uruguay
dc.description.fil
Fil: Veiga, Nicolás. Universidad de la República; Uruguay
dc.description.fil
Fil: Echeverría, Gustavo Alberto. Universidad Nacional de la Plata. Facultad de Ciencias Exactas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina
dc.description.fil
Fil: Piro, Oscar Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina
dc.description.fil
Fil: Faccio, Ricardo. Universidad de la República; Uruguay
dc.description.fil
Fil: Pérez Díaz, Leticia. Universidad de la República; Uruguay
dc.description.fil
Fil: Gasser, Gilles. Institute of Chemistry for Life and Health
Sciences. Laboratory for Inorganic Chemical Biology; Francia
dc.description.fil
Fil: Machado, Ignacio. Universidad de la República; Uruguay
dc.description.fil
Fil: Gambino, Dinorah. Universidad de la República; Uruguay
dc.journal.title
Dalton Transactions
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1039/d2dt03869b
Archivos asociados