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New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells
Author(s) -
Hyeraci Mariafrancesca,
Scalcon Valeria,
Folda Alessandra,
Labella Luca,
Marchetti Fabio,
Samaritani Simona,
Rigobello Maria Pia,
Dalla Via Lisa
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202100075
Subject(s) - cytotoxicity , ovarian carcinoma , intracellular , cisplatin , thioredoxin reductase , context (archaeology) , chemistry , ovarian cancer , dna damage , biochemistry , biology , cancer research , microbiology and biotechnology , in vitro , dna , thioredoxin , gene , cancer , chemotherapy , genetics , paleontology
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.