New heterobimetallic ferrocenyl derivatives: Evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium tuberculosis
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.jinorgbio.2018.07.013 http://hdl.handle.net/11449/180050 |
Resumo: | Searching for prospective agents against infectious diseases, four new ferrocenyl derivatives, [M(L)(dppf)4](PF6), with M = Pd(II) or Pt(II), dppf = 1,1′-bis(dipheny1phosphino) ferrocene and HL = tropolone (HTrop) or hinokitiol (HHino), were synthesized and characterized. Complexes and ligands were evaluated against the bloodstream form of T. brucei, L. infantum amastigotes, M. tuberculosis (MTB) sensitive strain and MTB clinical isolates. Complexes showed a significant increase of the anti-T. brucei activity with respect to the free ligands (>28- and >46-fold for Trop and 6- and 22-fold for Hino coordinated to Pt-dppf and Pd-dppf, respectively), yielding IC50 values < 5 μM. The complexes proved to be more potent than the antitrypanosomal drug Nifurtimox. The new ferrocenyl derivatives were more selective towards the parasite than the free ligands. The Pt compounds were less toxic on J774 murine macrophages (mammalian cell model), than the Pd ones, showing selectivity index values (SI = IC50 murine macrophage/IC50 T. brucei) up to 23. Generation of the {M-dppf} compounds lead to a slightly positive impact on the anti-leishmanial potency. Although the ferrocenyl derivatives were more active on sensitive MTB than the free ligands (MIC90 = 9.88–14.73 μM), they showed low selectivity towards the pathogen. Related to the mechanism of action, the antiparasitic effect cannot be ascribed to an interference of the compounds with the thiol-redox homeostasis of the pathogen. Fluorescence measurements pointed at DNA as a probable target of the new compounds. [Pt(Trop)(dppf)](PF6) and [Pt(Hino)(dppf)](PF6) could be considered prospective anti-T. brucei agents that deserve further research. |
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New heterobimetallic ferrocenyl derivatives: Evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium tuberculosisFerrocenyl compoundsLeishmaniasisMycobacterium tuberculosisTropolone derivativesTrypanosoma bruceiSearching for prospective agents against infectious diseases, four new ferrocenyl derivatives, [M(L)(dppf)4](PF6), with M = Pd(II) or Pt(II), dppf = 1,1′-bis(dipheny1phosphino) ferrocene and HL = tropolone (HTrop) or hinokitiol (HHino), were synthesized and characterized. Complexes and ligands were evaluated against the bloodstream form of T. brucei, L. infantum amastigotes, M. tuberculosis (MTB) sensitive strain and MTB clinical isolates. Complexes showed a significant increase of the anti-T. brucei activity with respect to the free ligands (>28- and >46-fold for Trop and 6- and 22-fold for Hino coordinated to Pt-dppf and Pd-dppf, respectively), yielding IC50 values < 5 μM. The complexes proved to be more potent than the antitrypanosomal drug Nifurtimox. The new ferrocenyl derivatives were more selective towards the parasite than the free ligands. The Pt compounds were less toxic on J774 murine macrophages (mammalian cell model), than the Pd ones, showing selectivity index values (SI = IC50 murine macrophage/IC50 T. brucei) up to 23. Generation of the {M-dppf} compounds lead to a slightly positive impact on the anti-leishmanial potency. Although the ferrocenyl derivatives were more active on sensitive MTB than the free ligands (MIC90 = 9.88–14.73 μM), they showed low selectivity towards the pathogen. Related to the mechanism of action, the antiparasitic effect cannot be ascribed to an interference of the compounds with the thiol-redox homeostasis of the pathogen. Fluorescence measurements pointed at DNA as a probable target of the new compounds. [Pt(Trop)(dppf)](PF6) and [Pt(Hino)(dppf)](PF6) could be considered prospective anti-T. brucei agents that deserve further research.Agencia Nacional de Investigación e InnovaciónÁrea Química Inorgánica Facultad de Química Universidad de la RepúblicaGroup Redox Biology of Trypanosomes Institut Pasteur MontevideoDepartamento de Bioquímica Facultad de Medicina Universidad de la RepúblicaFaculdade de Ciências Farmacêuticas UNESPFaculdade de Ciências Farmacêuticas UNESPAgencia Nacional de Investigación e Innovación: POS_NAC_2015_1_110215Agencia Nacional de Investigación e Innovación: POS_NAC_2016_1_129899Agencia Nacional de Investigación e Innovación: PR_FMV_2009_1_2617Universidad de la RepúblicaInstitut Pasteur MontevideoUniversidade Estadual Paulista (Unesp)Rivas, FeriannysMedeiros, AndreaRodríguez Arce, EstebanComini, MarceloRibeiro, Camila M. [UNESP]Pavan, Fernando R. [UNESP]Gambino, Dinorah2018-12-11T17:37:49Z2018-12-11T17:37:49Z2018-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article73-84application/pdfhttp://dx.doi.org/10.1016/j.jinorgbio.2018.07.013Journal of Inorganic Biochemistry, v. 187, p. 73-84.1873-33440162-0134http://hdl.handle.net/11449/18005010.1016/j.jinorgbio.2018.07.0132-s2.0-850503940222-s2.0-85050394022.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Inorganic Biochemistry0,743info:eu-repo/semantics/openAccess2024-06-24T13:06:45Zoai:repositorio.unesp.br:11449/180050Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T13:42:09.417678Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
New heterobimetallic ferrocenyl derivatives: Evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium tuberculosis |
title |
New heterobimetallic ferrocenyl derivatives: Evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium tuberculosis |
spellingShingle |
New heterobimetallic ferrocenyl derivatives: Evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium tuberculosis Rivas, Feriannys Ferrocenyl compounds Leishmaniasis Mycobacterium tuberculosis Tropolone derivatives Trypanosoma brucei |
title_short |
New heterobimetallic ferrocenyl derivatives: Evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium tuberculosis |
title_full |
New heterobimetallic ferrocenyl derivatives: Evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium tuberculosis |
title_fullStr |
New heterobimetallic ferrocenyl derivatives: Evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium tuberculosis |
title_full_unstemmed |
New heterobimetallic ferrocenyl derivatives: Evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium tuberculosis |
title_sort |
New heterobimetallic ferrocenyl derivatives: Evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium tuberculosis |
author |
Rivas, Feriannys |
author_facet |
Rivas, Feriannys Medeiros, Andrea Rodríguez Arce, Esteban Comini, Marcelo Ribeiro, Camila M. [UNESP] Pavan, Fernando R. [UNESP] Gambino, Dinorah |
author_role |
author |
author2 |
Medeiros, Andrea Rodríguez Arce, Esteban Comini, Marcelo Ribeiro, Camila M. [UNESP] Pavan, Fernando R. [UNESP] Gambino, Dinorah |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidad de la República Institut Pasteur Montevideo Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Rivas, Feriannys Medeiros, Andrea Rodríguez Arce, Esteban Comini, Marcelo Ribeiro, Camila M. [UNESP] Pavan, Fernando R. [UNESP] Gambino, Dinorah |
dc.subject.por.fl_str_mv |
Ferrocenyl compounds Leishmaniasis Mycobacterium tuberculosis Tropolone derivatives Trypanosoma brucei |
topic |
Ferrocenyl compounds Leishmaniasis Mycobacterium tuberculosis Tropolone derivatives Trypanosoma brucei |
description |
Searching for prospective agents against infectious diseases, four new ferrocenyl derivatives, [M(L)(dppf)4](PF6), with M = Pd(II) or Pt(II), dppf = 1,1′-bis(dipheny1phosphino) ferrocene and HL = tropolone (HTrop) or hinokitiol (HHino), were synthesized and characterized. Complexes and ligands were evaluated against the bloodstream form of T. brucei, L. infantum amastigotes, M. tuberculosis (MTB) sensitive strain and MTB clinical isolates. Complexes showed a significant increase of the anti-T. brucei activity with respect to the free ligands (>28- and >46-fold for Trop and 6- and 22-fold for Hino coordinated to Pt-dppf and Pd-dppf, respectively), yielding IC50 values < 5 μM. The complexes proved to be more potent than the antitrypanosomal drug Nifurtimox. The new ferrocenyl derivatives were more selective towards the parasite than the free ligands. The Pt compounds were less toxic on J774 murine macrophages (mammalian cell model), than the Pd ones, showing selectivity index values (SI = IC50 murine macrophage/IC50 T. brucei) up to 23. Generation of the {M-dppf} compounds lead to a slightly positive impact on the anti-leishmanial potency. Although the ferrocenyl derivatives were more active on sensitive MTB than the free ligands (MIC90 = 9.88–14.73 μM), they showed low selectivity towards the pathogen. Related to the mechanism of action, the antiparasitic effect cannot be ascribed to an interference of the compounds with the thiol-redox homeostasis of the pathogen. Fluorescence measurements pointed at DNA as a probable target of the new compounds. [Pt(Trop)(dppf)](PF6) and [Pt(Hino)(dppf)](PF6) could be considered prospective anti-T. brucei agents that deserve further research. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-11T17:37:49Z 2018-12-11T17:37:49Z 2018-10-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.jinorgbio.2018.07.013 Journal of Inorganic Biochemistry, v. 187, p. 73-84. 1873-3344 0162-0134 http://hdl.handle.net/11449/180050 10.1016/j.jinorgbio.2018.07.013 2-s2.0-85050394022 2-s2.0-85050394022.pdf |
url |
http://dx.doi.org/10.1016/j.jinorgbio.2018.07.013 http://hdl.handle.net/11449/180050 |
identifier_str_mv |
Journal of Inorganic Biochemistry, v. 187, p. 73-84. 1873-3344 0162-0134 10.1016/j.jinorgbio.2018.07.013 2-s2.0-85050394022 2-s2.0-85050394022.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Inorganic Biochemistry 0,743 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
73-84 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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_version_ |
1808128268715425792 |