Cargando…

New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells

Resistance to platinum‐based anticancer drugs represents an important limit for their clinical effectiveness and one of the most important field of investigation in the context of platinum compounds. From our previous studies, Pt(II) complexes containing the triphenylphosphino moiety have been emerg...

Descripción completa

Detalles Bibliográficos
Autores principales: Hyeraci, Mariafrancesca, Scalcon, Valeria, Folda, Alessandra, Labella, Luca, Marchetti, Fabio, Samaritani, Simona, Rigobello, Maria Pia, Dalla Via, Lisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252049/
https://www.ncbi.nlm.nih.gov/pubmed/33751814
http://dx.doi.org/10.1002/cmdc.202100075
_version_ 1783717219454156800
author Hyeraci, Mariafrancesca
Scalcon, Valeria
Folda, Alessandra
Labella, Luca
Marchetti, Fabio
Samaritani, Simona
Rigobello, Maria Pia
Dalla Via, Lisa
author_facet Hyeraci, Mariafrancesca
Scalcon, Valeria
Folda, Alessandra
Labella, Luca
Marchetti, Fabio
Samaritani, Simona
Rigobello, Maria Pia
Dalla Via, Lisa
author_sort Hyeraci, Mariafrancesca
collection PubMed
description Resistance to platinum‐based anticancer drugs represents an important limit for their clinical effectiveness and one of the most important field of investigation in the context of platinum compounds. From our previous studies, Pt(II) complexes containing the triphenylphosphino moiety have been emerging as promising agents, showing significant cytotoxicity to resistant ovarian carcinoma cells. Two brominated triphenylphosphino trans‐platinum derivatives were prepared and evaluated on human tumor cell lines, sensitive and resistant to cisplatin. The new complexes exert a notable antiproliferative effect on resistant ovarian carcinoma cells, showing a remarkable intracellular accumulation and the ability to interact with different intracellular targets. The interaction with DNA, the collapse of mitochondrial transmembrane potential, and the impairment of intracellular redox state were demonstrated. Moreover, a selectivity towards the selenocysteine of thioredoxin reductase was observed. The mechanism of action is discussed with regard to the resistance phenomenon in ovarian carcinoma cells.
format Online
Article
Text
id pubmed-8252049
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-82520492021-07-07 New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells Hyeraci, Mariafrancesca Scalcon, Valeria Folda, Alessandra Labella, Luca Marchetti, Fabio Samaritani, Simona Rigobello, Maria Pia Dalla Via, Lisa ChemMedChem Full Papers Resistance to platinum‐based anticancer drugs represents an important limit for their clinical effectiveness and one of the most important field of investigation in the context of platinum compounds. From our previous studies, Pt(II) complexes containing the triphenylphosphino moiety have been emerging as promising agents, showing significant cytotoxicity to resistant ovarian carcinoma cells. Two brominated triphenylphosphino trans‐platinum derivatives were prepared and evaluated on human tumor cell lines, sensitive and resistant to cisplatin. The new complexes exert a notable antiproliferative effect on resistant ovarian carcinoma cells, showing a remarkable intracellular accumulation and the ability to interact with different intracellular targets. The interaction with DNA, the collapse of mitochondrial transmembrane potential, and the impairment of intracellular redox state were demonstrated. Moreover, a selectivity towards the selenocysteine of thioredoxin reductase was observed. The mechanism of action is discussed with regard to the resistance phenomenon in ovarian carcinoma cells. John Wiley and Sons Inc. 2021-04-06 2021-06-17 /pmc/articles/PMC8252049/ /pubmed/33751814 http://dx.doi.org/10.1002/cmdc.202100075 Text en © 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Full Papers
Hyeraci, Mariafrancesca
Scalcon, Valeria
Folda, Alessandra
Labella, Luca
Marchetti, Fabio
Samaritani, Simona
Rigobello, Maria Pia
Dalla Via, Lisa
New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells
title New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells
title_full New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells
title_fullStr New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells
title_full_unstemmed New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells
title_short New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells
title_sort new platinum(ii) complexes affecting different biomolecular targets in resistant ovarian carcinoma cells
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252049/
https://www.ncbi.nlm.nih.gov/pubmed/33751814
http://dx.doi.org/10.1002/cmdc.202100075
work_keys_str_mv AT hyeracimariafrancesca newplatinumiicomplexesaffectingdifferentbiomoleculartargetsinresistantovariancarcinomacells
AT scalconvaleria newplatinumiicomplexesaffectingdifferentbiomoleculartargetsinresistantovariancarcinomacells
AT foldaalessandra newplatinumiicomplexesaffectingdifferentbiomoleculartargetsinresistantovariancarcinomacells
AT labellaluca newplatinumiicomplexesaffectingdifferentbiomoleculartargetsinresistantovariancarcinomacells
AT marchettifabio newplatinumiicomplexesaffectingdifferentbiomoleculartargetsinresistantovariancarcinomacells
AT samaritanisimona newplatinumiicomplexesaffectingdifferentbiomoleculartargetsinresistantovariancarcinomacells
AT rigobellomariapia newplatinumiicomplexesaffectingdifferentbiomoleculartargetsinresistantovariancarcinomacells
AT dallavialisa newplatinumiicomplexesaffectingdifferentbiomoleculartargetsinresistantovariancarcinomacells