Multi-target heteroleptic palladium bisphosphonate complexes

Autores
Cipriani, Micaella; Rostán, Santiago; León, Ignacio Esteban; Li, Zhu-Hong; Gancheff, Jorge S.; Kemmerling, Ulrike; Olea Azar, Claudio; Etcheverry, Susana Beatriz; Docampo, Roberto; Gambino, Dinorah; Otero, Lucía
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Bisphosphonates are the most commonly prescribed drugs for the treatment of osteoporosis and other bone illnesses. Some of them have also shown antiparasitic activity. In search of improving the pharmacological profile of commercial bisphosphonates, our group had previously developed first row transition metal complexes with N-containing bisphosphonates (NBPs). In this work, we extended our studies to heteroleptic palladium–NBP complexes including DNA intercalating polypyridyl co-ligands (NN) with the aim of obtaining potential multi-target species. Complexes of the formula [Pd(NBP)₂(NN)]·2NaCl·xH₂O with NBP = alendronate (ale) or pamidronate (pam) and NN = 1,10 phenanthroline (phen) or 2,2′-bipyridine (bpy) were synthesized and fully characterized. All the obtained compounds were much more active in vitro against T. cruzi (amastigote form) than the corresponding NBP ligands. In addition, complexes were nontoxic to mammalian cells up to 50–100 µM. Compounds with phen as ligand were 15 times more active than their bpy analogous. Related to the potential mechanism of action, all complexes were potent inhibitors of two parasitic enzymes of the isoprenoid biosynthetic pathway. No correlation between the anti-T. cruzi activity and the enzymatic inhibition results was observed. On the contrary, the high antiparasitic activity of phen-containing complexes could be related to their ability to interact with DNA in an intercalative-like mode. These rationally designed compounds are good candidates for further studies and good leaders for future drug developments. Four new palladium heteroleptic complexes with N-containing commercial bisphosphonates and DNA intercalating polypyridyl co-ligands were synthesized and fully characterized. All complexes displayed high anti-T. cruzi activity which could be related to the inhibition of the parasitic farnesyl diphosphate synthase enzyme but mainly to their ability to interact DNA.
Centro de Química Inorgánica
Materia
Química
Biología
Bisphosphonate
Palladium
DNA
Chagas
Toxoplasmosis
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/136986

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network_name_str SEDICI (UNLP)
spelling Multi-target heteroleptic palladium bisphosphonate complexesCipriani, MicaellaRostán, SantiagoLeón, Ignacio EstebanLi, Zhu-HongGancheff, Jorge S.Kemmerling, UlrikeOlea Azar, ClaudioEtcheverry, Susana BeatrizDocampo, RobertoGambino, DinorahOtero, LucíaQuímicaBiologíaBisphosphonatePalladiumDNAChagasToxoplasmosisBisphosphonates are the most commonly prescribed drugs for the treatment of osteoporosis and other bone illnesses. Some of them have also shown antiparasitic activity. In search of improving the pharmacological profile of commercial bisphosphonates, our group had previously developed first row transition metal complexes with N-containing bisphosphonates (NBPs). In this work, we extended our studies to heteroleptic palladium–NBP complexes including DNA intercalating polypyridyl co-ligands (NN) with the aim of obtaining potential multi-target species. Complexes of the formula [Pd(NBP)₂(NN)]·2NaCl·xH₂O with NBP = alendronate (ale) or pamidronate (pam) and NN = 1,10 phenanthroline (phen) or 2,2′-bipyridine (bpy) were synthesized and fully characterized. All the obtained compounds were much more active in vitro against <i>T. cruzi</i> (amastigote form) than the corresponding NBP ligands. In addition, complexes were nontoxic to mammalian cells up to 50–100 µM. Compounds with phen as ligand were 15 times more active than their bpy analogous. Related to the potential mechanism of action, all complexes were potent inhibitors of two parasitic enzymes of the isoprenoid biosynthetic pathway. No correlation between the anti-<i>T. cruzi</i> activity and the enzymatic inhibition results was observed. On the contrary, the high antiparasitic activity of phen-containing complexes could be related to their ability to interact with DNA in an intercalative-like mode. These rationally designed compounds are good candidates for further studies and good leaders for future drug developments. Four new palladium heteroleptic complexes with N-containing commercial bisphosphonates and DNA intercalating polypyridyl co-ligands were synthesized and fully characterized. All complexes displayed high anti-<i>T. cruzi</i> activity which could be related to the inhibition of the parasitic farnesyl diphosphate synthase enzyme but mainly to their ability to interact DNA.Centro de Química Inorgánica2020-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf509-519http://sedici.unlp.edu.ar/handle/10915/136986enginfo:eu-repo/semantics/altIdentifier/issn/1432-1327info:eu-repo/semantics/altIdentifier/issn/0949-8257info:eu-repo/semantics/altIdentifier/doi/10.1007/s00775-020-01779-yinfo:eu-repo/semantics/altIdentifier/pmid/32232584info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:32:32Zoai:sedici.unlp.edu.ar:10915/136986Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:32:32.912SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Multi-target heteroleptic palladium bisphosphonate complexes
title Multi-target heteroleptic palladium bisphosphonate complexes
spellingShingle Multi-target heteroleptic palladium bisphosphonate complexes
Cipriani, Micaella
Química
Biología
Bisphosphonate
Palladium
DNA
Chagas
Toxoplasmosis
title_short Multi-target heteroleptic palladium bisphosphonate complexes
title_full Multi-target heteroleptic palladium bisphosphonate complexes
title_fullStr Multi-target heteroleptic palladium bisphosphonate complexes
title_full_unstemmed Multi-target heteroleptic palladium bisphosphonate complexes
title_sort Multi-target heteroleptic palladium bisphosphonate complexes
dc.creator.none.fl_str_mv Cipriani, Micaella
Rostán, Santiago
León, Ignacio Esteban
Li, Zhu-Hong
Gancheff, Jorge S.
Kemmerling, Ulrike
Olea Azar, Claudio
Etcheverry, Susana Beatriz
Docampo, Roberto
Gambino, Dinorah
Otero, Lucía
author Cipriani, Micaella
author_facet Cipriani, Micaella
Rostán, Santiago
León, Ignacio Esteban
Li, Zhu-Hong
Gancheff, Jorge S.
Kemmerling, Ulrike
Olea Azar, Claudio
Etcheverry, Susana Beatriz
Docampo, Roberto
Gambino, Dinorah
Otero, Lucía
author_role author
author2 Rostán, Santiago
León, Ignacio Esteban
Li, Zhu-Hong
Gancheff, Jorge S.
Kemmerling, Ulrike
Olea Azar, Claudio
Etcheverry, Susana Beatriz
Docampo, Roberto
Gambino, Dinorah
Otero, Lucía
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Química
Biología
Bisphosphonate
Palladium
DNA
Chagas
Toxoplasmosis
topic Química
Biología
Bisphosphonate
Palladium
DNA
Chagas
Toxoplasmosis
dc.description.none.fl_txt_mv Bisphosphonates are the most commonly prescribed drugs for the treatment of osteoporosis and other bone illnesses. Some of them have also shown antiparasitic activity. In search of improving the pharmacological profile of commercial bisphosphonates, our group had previously developed first row transition metal complexes with N-containing bisphosphonates (NBPs). In this work, we extended our studies to heteroleptic palladium–NBP complexes including DNA intercalating polypyridyl co-ligands (NN) with the aim of obtaining potential multi-target species. Complexes of the formula [Pd(NBP)₂(NN)]·2NaCl·xH₂O with NBP = alendronate (ale) or pamidronate (pam) and NN = 1,10 phenanthroline (phen) or 2,2′-bipyridine (bpy) were synthesized and fully characterized. All the obtained compounds were much more active in vitro against <i>T. cruzi</i> (amastigote form) than the corresponding NBP ligands. In addition, complexes were nontoxic to mammalian cells up to 50–100 µM. Compounds with phen as ligand were 15 times more active than their bpy analogous. Related to the potential mechanism of action, all complexes were potent inhibitors of two parasitic enzymes of the isoprenoid biosynthetic pathway. No correlation between the anti-<i>T. cruzi</i> activity and the enzymatic inhibition results was observed. On the contrary, the high antiparasitic activity of phen-containing complexes could be related to their ability to interact with DNA in an intercalative-like mode. These rationally designed compounds are good candidates for further studies and good leaders for future drug developments. Four new palladium heteroleptic complexes with N-containing commercial bisphosphonates and DNA intercalating polypyridyl co-ligands were synthesized and fully characterized. All complexes displayed high anti-<i>T. cruzi</i> activity which could be related to the inhibition of the parasitic farnesyl diphosphate synthase enzyme but mainly to their ability to interact DNA.
Centro de Química Inorgánica
description Bisphosphonates are the most commonly prescribed drugs for the treatment of osteoporosis and other bone illnesses. Some of them have also shown antiparasitic activity. In search of improving the pharmacological profile of commercial bisphosphonates, our group had previously developed first row transition metal complexes with N-containing bisphosphonates (NBPs). In this work, we extended our studies to heteroleptic palladium–NBP complexes including DNA intercalating polypyridyl co-ligands (NN) with the aim of obtaining potential multi-target species. Complexes of the formula [Pd(NBP)₂(NN)]·2NaCl·xH₂O with NBP = alendronate (ale) or pamidronate (pam) and NN = 1,10 phenanthroline (phen) or 2,2′-bipyridine (bpy) were synthesized and fully characterized. All the obtained compounds were much more active in vitro against <i>T. cruzi</i> (amastigote form) than the corresponding NBP ligands. In addition, complexes were nontoxic to mammalian cells up to 50–100 µM. Compounds with phen as ligand were 15 times more active than their bpy analogous. Related to the potential mechanism of action, all complexes were potent inhibitors of two parasitic enzymes of the isoprenoid biosynthetic pathway. No correlation between the anti-<i>T. cruzi</i> activity and the enzymatic inhibition results was observed. On the contrary, the high antiparasitic activity of phen-containing complexes could be related to their ability to interact with DNA in an intercalative-like mode. These rationally designed compounds are good candidates for further studies and good leaders for future drug developments. Four new palladium heteroleptic complexes with N-containing commercial bisphosphonates and DNA intercalating polypyridyl co-ligands were synthesized and fully characterized. All complexes displayed high anti-<i>T. cruzi</i> activity which could be related to the inhibition of the parasitic farnesyl diphosphate synthase enzyme but mainly to their ability to interact DNA.
publishDate 2020
dc.date.none.fl_str_mv 2020-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/136986
url http://sedici.unlp.edu.ar/handle/10915/136986
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1432-1327
info:eu-repo/semantics/altIdentifier/issn/0949-8257
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00775-020-01779-y
info:eu-repo/semantics/altIdentifier/pmid/32232584
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
509-519
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
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